bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of gastric emptying by acids depends on pH, titratable acidity, and length of intestine exposed to acid
Authors: Lin H. C. , Doty J. E. , Reedy T. J. , Meyer J. H.
Published: December 2017

Exposure of the small intestine to acid inhibits gastric emptying in a dose-related fashion that depends on titratable acidity and pH. Little information is available on the location of this inhibitory mechanism or on the relative contribution of titratable acidity and pH to this feedback control. We hypothesized that the dependence on titratable acidity is related to the length of the intestine exposed to acid and that the dependence on pH is related to the region of the intestine exposed to acid. To test these ideas, we studied 11 dogs with duodenal and jejunal fistulas. The inhibitory effects were tested when different lengths of the small intestine were exposed to test solutions of 0.03, 0.06, and 0.12 meq/ml titratable acidities. pH as an independent covariable was separated from titratable acidity by comparing the inhibition of gastric emptying of lactic acid (pH fixed to 2.4) to HCl (pH 0.96-1.6). Maximal inhibition of gastric emptying by both acids depended on acid exposure of a length of small intestine that was greater than 65 but less than or equal to 150 cm long. When acid was confined to the proximal 15 cm, increasing concentration of HCl (decreasing pH) resulted in increasing inhibition, but this effect was absent with increasing concentration of lactic acid (fixed pH). Inhibition was absent when 0.06 meq/ml HCl was infused into the intestine beyond the midintestine.(ABSTRACT TRUNCATED AT 250 WORDS)
Feeding induces lipid accumulation and increased Na+ transport in in vitro Necturus antrum
Authors: Rutten M. J. , Moore C. D. , Delcore R. , Cheung L. Y.
Published: December 2017

We investigated the effects of feeding on lipid accumulation and transepithelial transport using in vitro Necturus gastric antral mucosae. Antra from fed Necturi were examined for lipid accumulation using light, fluorescence, histochemical, and electron microscopy. Ussing chambers were used for measurement of potential difference (PD), transepithelial resistance (Rt), short-circuit current (Isc), and unidirectional fluxes of 22Na+ and [3H]mannitol. Light microscopy of antra from 2-day postfed animals showed many intracellular lipid granules in surface mucous epithelial cells. These granules could be distinguished from other intracellular organelles by their high affinity for osmium and the lipid fluorescent probe Nile red. Glycoprotein cytochemical staining showed these granules to be distinct from the epithelial cell mucous granules. Electron microscopy showed the lipid granules to be part of a membranous reticular network. Two-day postfed animals also had a approximately 3.5-fold increase in amiloride-sensitive Isc and PD, a decrease in Rt, and an increased luminal-to-serosal Na+ fluxes. Transepithelial [3H]mannitol fluxes were low and remained unchanged in both fasted and 2-day postfed animals. After 2 days of feeding, the PD and Isc began to decrease followed by a secondary increase in Rt. Feeding Necturi a corn oil diet did not induce the appearance of either cellular lipid or alterations in Isc but produced a transient increase in Rt. Our data show that feeding (goldfish) to Necturi causes an increase in both lipid accumulation and amiloride-sensitive Na+ transport in gastric antral cells.
Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers
Authors: Strazzabosco M. , Sakisaka S. , Hayakawa T. , Boyer J. L.
Published: December 2017

To study how ursodeoxycholic acid (UDCA) increases biliary HCO3- concentration and alkalinizes bile, intracellular pH (pHi) and canalicular pH (pHc) were measured microfluorimetrically in isolated rat hepatocyte couplets (IRHC). Isolated perfused rat livers (IPRL) were also used to assess the roles of Cl-, HCO3-, and zone III hepatocytes. In IRHC, UDCA diminished pHi only when HCO3- was omitted. pHi recovery was inhibited by amiloride. UDCA did not affect pHi recovery from an acid load (NH4Cl) nor modify pHc (+HCO3-). In IPRL, biliary HCO3- concentration increased following UDCA despite removal of Cl- (to inhibit Cl(-)-HCO3- exchanger) or destruction of zone III hepatocytes with digitonin. Moreover, when HCO3- was omitted from the perfusate, biliary pH rose following UDCA even though the hypercholeresis was abolished. Thus 1) hepatic UDCA uptake represents an acid load that is counteracted by Na(+)-H+ exchange when HCO3- is absent; 2) UDCA does not alkalinize pHc; and 3) alkalinization of biliary pH in IPRL is not HCO3- dependent, does not involve Cl(-)-HCO3- exchange, or zonal differences in UDCA metabolism or excretion. UDCA appears to alkalinize bile by protonation within the bile duct lumen. UDCAH may then cross the biliary epithelium.
Effects of CCK receptor blockade on intestinal motor activity in conscious dogs
Authors: Niederau C. , Karaus M.
Published: December 2017

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the small intestine. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by six strain-gauge transducers implanted along the small intestine. The effects of the CCK analogue caerulein and the CCK antagonist loxiglumide were studied in fasted and fed states. Computer analysis determined contractile frequency and area under contractions. Caerulein given as an intravenous bolus 30 min after phase III dose dependently caused a burst of phasic contractions preceded by a retrograde giant contraction. Continuous intravenous infusion of 10 mg.kg-1.h-1 loxiglumide completely abolished the effects of 10 ng/kg caerulein, which increases plasma CCK immunoreactivity to postprandial levels. Loxiglumide, at 10 mg.kg-1.h-1, markedly reduced the increase in phasic contractions due to a supraphysiological dose of 50 ng/kg caerulein to 14 +/- 6(SD)% of the control without loxiglumide (P less than 0.01). The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms/kg) was not altered by loxiglumide. Loxiglumide given in the fasted state decreased contractile frequency from 9.5 +/- 0.7 to 8.1 +/- 0.6/min and reduced the area under contractions during phase II to 81 +/- 5% of the control without loxiglumide (P less than 0.05). Loxiglumide also decreased contractile frequency during the fed state from 9.7 +/- 0.6 to 8.3 +/- 0.5/min and reduced the area under contractions to 78 +/- 6% of the control without loxiglumide (P less than 0.05). Thus loxiglumide acts as a specific antagonist of the actions of CCK on small intestinal motor activity in the dog. Loxiglumide, at a dose that abolishes actions of endogenous CCK, significantly decreased fasting motor activity during phase II. Loxiglumide also significantly reduced motor responses to feeding but did not prevent interruption of migrating motor complex cycle by a meal. CCK plays a physiological role in regulation of fasting and fed motor activity of small intestine, although other factors in addition to CCK mediate meal-induced motor activity.
pH-sensitive anion exchanger in rat lacrimal acinar cells
Authors: Lambert R. W. , Bradley M. E. , Mircheff A. K.
Published: December 2017

Basolateral membranes from rat lacrimal acinar cells contain Na(+)-H+ and Cl(-)-HCO3- antiport activities [Invest. Ophthalmol. Visual Sci. 28: 1726-1729, 1989; Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 18): G367-G373, 1988]. This study evaluated factors involved in coupling ion fluxes through these antiporters. 22Na+ flux into acini isolated from rat exorbital glands was 94 +/- 6 nmol.mg-1.min-1, and it was accelerated threefold by 10(-5) M carbachol; neither resting nor stimulated influx was affected by bumetanide. It is, therefore, likely that a portion of the carbachol-dependent Na+ influx is mediated by Na(+)-H+ antiporters. 36Cl- flux into Cl(-)-loaded, unstimulated acini was 275 +/- 21 nmol.mg-1.min-1; Cl- flux into HCO3(-)-loaded acini was 204 +/- 2; Cl- flux into acini loaded with both Cl- and HCO3- was 253 +/- 32; and influx in the absence of exchangeable intracellular anions was 176 +/- 13. Therefore, Cl(-)-Cl- self-exchange represented the major component of anion exchanger-mediated Cl- flux into resting cells. As pHi was increased above 7.2 by potassium-nigericin pH clamping, Cl- fluxes into Cl(-)- and HCO3(-)-containing acini, but not into Cl(-)-depleted acini, were significantly accelerated. SITS completely abolished the pHi-activated increment of Cl(-)-Cl- exchange. Carbachol increased Cl- unidirectional flux into Cl(-)-loaded cells by 25% (P less than 0.1), apparently as a result of Na(+)-H+ antiporter-mediated cytoplasmic alkalinization.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of polyamines in gastrointestinal mucosal growth
Authors: McCormack S. A. , Johnson L. R.
Published: December 2017

The polyamines have been under active investigation for nearly three decades. There is a great deal of evidence that they play an important role in gastrointestinal mucosal growth, but the mechanisms through which this role is carried out are still not fully explained. This review examines the role of the polyamines in the regulation of mucosal growth, the control of intracellular polyamine levels, the biosynthesis of the polyamines, and some known mechanisms of their action. Finally, we propose a model of polyamine action that reconciles the effects of various trophic agents and situations in which growth is stimulated along with concomitant changes in polyamine levels. It accounts for both humoral and gradient-oriented features of various adaptive responses of the gastrointestinal mucosa and is intended to provide a framework for the future investigation of the role of the polyamines in this tissue.
Monochloramine induces contraction of guinea pig gallbladder via two different pathways
Authors: Moummi C. , Gullikson G. W. , Gaginella T. S.
Published: December 2017

The purpose of the present investigation was to examine the effect and mechanism of action of the reactive oxygen metabolites monochloramine (NH2Cl), hypochlorous acid (HOCl), and hydrogen peroxide (H2O2) on gallbladder smooth muscle contractility. All oxidants caused concentration-dependent increases in resting tension of gallbladder muscle; the rank order of potencies (half-maximal concentration) was NH2Cl (30 microM) greater than HOCl (70 microM) greater than H2O2 (100 microM). The oxidant concentrations employed are those found to exist in inflamed tissue. Tetrodotoxin (0.5 microM) had no effect on gallbladder muscle contraction caused by the oxidants, suggesting a direct, nonneural action. The maximal response induced by NH2Cl, HOCl, or H2O2 was significantly (P less than 0.05) inhibited by 5 microM indomethacin and 5 microM piroxicam. The calcium channel blocker verapamil partially inhibited the contractile effect of NH2Cl but had no effect on the contraction induced by exogenous cyclooxygenase products. Monochloramine induced significant prostaglandin E2 release from the gallbladder, which was blocked by indomethacin. Furthermore, the effect of NH2Cl on the smooth muscle was blocked by 5-aminosalicylic acid (1 mM). We conclude that reactive oxygen metabolites induce contraction of gallbladder smooth muscle by a direct action. The effect is mediated via cyclooxygenase metabolites and activation of calcium influx.
Effects of hypoxia and ischemia on autoregulation in postnatal intestine
Authors: Nowicki P. T. , Miller C. E. , Edwards R. C.
Published: December 2017

Pressure-flow autoregulation was quantified within in vitro intestine from 3- and 35-day-old swine before and after lowering arterial PO2 (hypoxia) or lowering baseline blood flow by means of norepinephrine infusion (ischemia). Autoregulation was elicited by reducing arterial pressure approximately 33% from an age-appropriate baseline pressure. In 3-day-old intestine, autoregulation was unaffected by hypoxia or ischemia: vascular resistance was unchanged after pressure reduction, while Gf averaged -0.33 +/- 0.15 vs. -0.26 +/- 0.05 under control vs. hypoxic conditions, and -0.48 +/- 0.15 vs. -0.46 +/- 0.11 under control vs. ischemic conditions, respectively. In 35-day-old intestine, autoregulation was enhanced by hypoxia and ischemia. Under both experimental conditions, vasodilation was noted in response to pressure reduction: Gf averaged -0.04 +/- 0.14 vs. 0.38 +/- 0.08 under control vs. hypoxic conditions, and -0.12 +/- 0.10 vs. 0.28 +/- 0.08 under control vs. ischemic conditions, respectively. Regression analysis revealed a significant inverse linear correlation between Gf and venous PO2 in older, but not younger, subjects. Significant relationships between Gf and blood flow were not demonstrated in either group under any experimental condition. We conclude that autoregulation is enhanced within in vitro intestine from 35-, but not 3-day-old, swine during hypoxia or ischemia, and that reduction of venous PO2 is the principal factor responsible for the effect noted in older subjects.
Adaptive regulation of brush-border amino acid transport in a chronic excluded jejunal limb
Authors: Salloum R. M. , Stevens B. R. , Souba W. W.
Published: December 2017

We examined the alterations in brush-border glutamine transport that occurred in a surgically defunctionalized jejunal limb excluded from mucosal food contact. Dogs were surgically prepared with Roux-en-Y gastrojejunostomies to permit same-intestine comparisons of glutamine transport and glutaminase activity in jejunal segments that were in incontinuity or excluded for a 6-mo period. Transport of glutamine, alanine, and glucose was measured in brush-border membrane vesicles prepared from each intestinal section; membrane marker enzymes were enriched to the same degree in incontinuity and excluded portions. The Na(+)-dependent glutamine cotransport apparent Km was the same in the excluded (779 +/- 63 microM) and incontinuity (873 +/- 105 microM) limbs. However, the Jmax for Na(+)-independent glutamine transport in the incontinuity jejunum (158.7 +/- 15.7 pmol.mg protein-1.s-1) was double that in the excluded limb (71.2 +/- 4.6 pmol.mg protein-1.s-1). Na(+)-dependent carrier-mediated glutamine transport rates were lower than the Na(+)-dependent system, but Na(+)-independent kinetic parameters were not significantly different in incontinuity vs. excluded limbs (Jmax 7.9 +/- 0.6 pmol.mg protein-1.s-1; Km 140 +/- 20 microM). Similarly, the passive diffusion permeability coefficient was the same for both excluded and incontinuity jejunal limbs (22.7 +/- 0.9 nl.mg protein-1.s-1). Mucosal glutaminase enzyme activity was increased by 28% in the incontinuity limb (4.32 +/- 0.21 vs. 3.36 +/- 0.35 mumol.mg protein-1.h-1; P less than 0.02). Transport rates of alanine and glucose were also diminished in the excluded limb (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of oxygen-derived free radicals in indomethacin-induced gastric injury
Authors: Vaananen P. M. , Meddings J. B. , Wallace J. L.
Published: December 2017

The role of oxygen-derived free radicals in the pathogenesis of acute gastric ulceration induced by indomethacin (Indo) was investigated in rats. Gastric damage was assessed by blood-to-lumen leakage of 51Cr-EDTA, as well as by measuring the extent of macroscopically visible hemorrhagic lesions. The stomach was perfused with isotonic saline for 30 min, followed by Indo (10 mg/ml for 30 min) and HCl (100 mM for 60 min). Rats were given a continuous intravenous infusion of the antioxidant enzymes superoxide dismutase (SOD) or catalase or the iron-chelating agent deferoxamine. Additional rats received an intravenous infusion of the vehicle (control group) or were pretreated with prostaglandin E2 (100 micrograms/kg ip) or allopurinol (50 mg/kg po). Exposure of the stomach to Indo caused a fourfold increase in 51Cr-EDTA leakage compared with that observed in rats receiving only the vehicle for Indo. Subsequent exposure of the stomach to HCl resulted in a further twofold increase in 51Cr-EDTA leakage. Treatment with SOD, catalase, or deferoxamine significantly (P less than 0.05) reduced 51Cr-EDTA leakage during the intragastric perfusion with Indo and during the subsequent exposure to HCl. Pretreatment with PGE2 reduced 51Cr-EDTA leakage during perfusion with HCl only. Pretreatment with allopurinol did not significantly affect 51Cr-EDTA leakage at any time during the experiment. In addition to reducing the leakage of 51Cr-EDTA into the gastric lumen, SOD, catalase, and PGE2 significantly reduced the extent of macroscopically visible mucosal damage (P less than 0.05). These results support the hypothesis that oxygen-derived free radicals, probably derived from neutrophils, contribute to the pathogenesis of Indo-induced ulceration.
Role of calcitonin gene-related peptide in gastric hyperemic response to intragastric capsaicin
Authors: Li D. S. , Raybould H. E. , Quintero E. , Guth P. H.
Published: December 2017

Stimulation of sensory neurons in the rat stomach by intragastric capsaicin leads to a marked rise in gastric mucosal blood flow (GMBF). The gastric mucosa, in particular submucosal blood vessels, is densely innervated by afferent neurons containing peptides, of which calcitonin gene-related peptide (CGRP) is the most potent vasodilator. Using selective ablation of either the vagal or spinal sensory innervation to the stomach by perineural application of capsaicin, and by intra-arterial infusion of the CGRP receptor antagonist hCGRP-(8-37) close to the stomach, we investigated 1) the origin (vagal or spinal) of the sensory neurons and 2) whether CGRP mediates this hyperemic response. Perivagal application of capsaicin to the rat 10-20 days before experiments had no effect on the hyperemic response to intragastric capsaicin. In contrast, periceliac application of capsaicin significantly reduced this response by 60%. Intra-arterial infusion of CGRP (20 pmol/min) close to the stomach produced a marked rise in GMBF and this was completely blocked by hCGRP-(8-37) (500 pmol/min). intra-arterial infusion of hCGRP-(8-37) or its vehicle, bovine serum albumin, had no significant effect on basal GMBF. However, the increment in GMBF in response to intragastric capsaicin was significantly attenuated by 79%. We conclude that 1) spinal sensory neurons innervating the gastric mucosa partially mediate the increase in GMBF induced by intragastric capsaicin and 2) CGRP is the major vasodilator released by these fibers.
Evidence for a glutamatergic neural pathway in the myenteric plexus
Authors: Wiley J. W. , Lu Y. X. , Owyang C.
Published: December 2017

The objective of this study was to determine whether L-glutamate (L-Glu) may serve as a neurotransmitter candidate in the guinea pig myenteric plexus. We observed that [3H]Glu and gamma-[3H]aminobutyric acid were synthesized from [3H]glutamine and released from neurons of the myenteric plexus during K+ and 1,1-dimethyl-4-phenylpiperazinium-evoked depolarization in a concentration-dependent manner. Muscle tension studies performed on ileal longitudinal muscle-myenteric plexus (LM-MP) preparations revealed that L-Glu [mean effective dose (ED50) 2.5 x 10(-5) M] produced concentration-dependent contractions, which were unaffected by hexamethonium but abolished by tetrodotoxin, atropine, and magnesium, suggesting that L-Glu acts via N-methyl-D-aspartate (NMDA)-type receptors that stimulate a cholinergic neural pathway unaffected by ganglionic blockade. In addition, L-Glu (ED50 4 x 10(-5) M) and NMDA (ED50 2 x 10(-4) M) stimulated concentration-dependent release of [3H]acetylcholine (ACh) from LM-MP sections, which was inhibited by tetrodotoxin, magnesium, and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP-5). L-Glu-mediated release of [3H]ACh was enhanced by theophylline (10-6 M) and 3-isobutyl-1-methylxanthine (1 mM) and was significantly reduced by the adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (10(-4) M) and somatostatin-14 (10(-6) M), which inhibits adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cholinergic transmission in the myenteric plexus. These studies suggest that L-Glu may serve as an excitatory neurotransmitter in the myenteric plexus via its action on NMDA-type receptors, which are coupled to cAMP-dependent release of ACh.
Ca2+ and cAMP activate different chloride efflux pathways in HT-29.cl19A colonic epithelial cell line
Authors: Vaandrager A. B. , Bajnath R. , Groot J. A. , Bot A. G. , De Jonge H. R.
Published: December 2017

The mechanism of adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca(2+)-induced Cl- secretion was studied in monolayers of the colon carcinoma cell line HT-29.cl19A by combined short-circuit current (Isc) and 125I- or 36Cl- efflux measurements. Forskolin, a specific adenylate cyclase activator, was found to induce a large increase in Isc and a two- to threefold increase in 36Cl- efflux solely across the apical border. The fractional efflux of 36Cl-compared with 125I- (basal ratio 1.71 +/- 0.28) did not change significantly in the presence of forskolin (1.91 +/- 0.45). In contrast, the Ca2+ ionophore A23187 did not appreciably affect the Isc but enhanced 36Cl- and 125I- efflux at the apical and basolateral side of the monolayer. Furthermore, the fractional efflux ratio of 36Cl- to 125I- changed dramatically to a value of 0.36 +/- 0.14. Both forskolin- and A23187-induced 36Cl- or 125I- efflux were only weakly inhibited by the putative Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoicacid. Carbachol, a Ca(2+)-linked agonist, mimicked the effects of A23187 on the 36Cl- and 125I- efflux but additionally provoked a significant increase in Isc. These data show that Ca2+ and cAMP activate different Cl-efflux pathways in HT-29.cl19A cells. Most likely these pathways represent a cAMP-activated conductance in the apical membrane and a separate Ca(2+)-activated Cl- conductance expressed in both apical and basolateral membranes. Apparently cholinergic agonists induce net electrogenic Cl- secretion through an intracellular signaling pathway (e.g., protein kinase C activation) different from the one activated by Ca2+/Ca2+ ionophore alone.
Electrical and mechanical effects of acetylcholine and substance P in subregions of canine colon
Authors: Keef K. D. , Ward S. M. , Stevens R. J. , Frey B. W. , Sanders K. M.
Published: December 2017

Effects of acetylcholine (ACh) and substance P on the electrical and mechanical activities of the circular muscle layer of the canine proximal colon were studied. Because this muscle layer is bordered by two different pacemaker regions, responses from segments containing either a single pacemaker region or no pacemaker region were compared with responses of the complete muscle layer. Concentration-response relationships for ACh and substance P were similar between the various segments, suggesting that receptors for these agonists are expressed throughout the layer. The dominant contractile pattern induced by ACh and substance P in each segment was a 1- to 3-cycle/min rhythm. In a like manner, these agonists also elicited an electrical pattern in which a long-duration slow wave occurred one to three times per minute between short-duration slow waves. Low concentrations of nifedipine (0.01 microM) selectively antagonized the 1- to 3-cycle/min rhythm. In circular muscles with no pacemaker region, ACh (1 microM) caused depolarization, induced oscillations in membrane potential averaging 24 +/- 5 mV in amplitude and 2.9 +/- 0.9 cycles/min in frequency, and generated rhythmic contractions at the same frequency. This "interior" circular muscle was functionally innervated by cholinergic excitatory nerves. Exposure to ACh (1 microM) did not alter the conduction of slow waves through the thickness of the circular layer. In summary, the excitatory neurotransmitters, ACh and substance P, induce a dominant electrical and contractile rhythm throughout the circular muscle layer that is different from the spontaneous rhythms produced at either the myenteric or submucosal border.
Closure mechanisms of laryngeal vestibule during swallow
Authors: Logemann J. A. , Kahrilas P. J. , Cheng J. , Pauloski B. R. , Gibbons P. J. , Rademaker A. W. , Lin S.
Published: December 2017

This study examined the temporal effects of bolus volume on closure of the laryngeal vestibule at the arytenoid to epiglottic base and the mobile portion of the epiglottis, the temporal relationships between these levels of airway closure and cricopharyngeal opening for various bolus volumes, and the mechanisms responsible for these two levels of airway protection during deglutition. Closure of the laryngeal vestibule progressed inferiorly to superiorly at all bolus volumes. Duration of closure of the airway at the arytenoid to epiglottic base increased systematically with bolus volume, as did the duration of descent of the epiglottis below horizontal. Closure at the arytenoid to epiglottic base occurred earlier in relation to maximal laryngeal elevation as bolus volume increased. In contrast, descent of the epiglottis to horizontal and the temporal relationship between closure of the airway at the arytenoid to epiglottic base and cricopharyngeal opening were independent of bolus volume. These findings indicate a tightly organized neural program for some pharyngeal swallow events with systematic variability with volume in other pharyngeal events, possibly modulated by afferent input from the periphery. The neuromuscular mechanisms responsible for closure of the airway at the arytenoid to epiglottic base and at the mobile epiglottis appear to be quite different. Closure at the arytenoid to epiglottic base is apparently under direct neural control by active anterior tilting of the arytenoid cartilage and posterior projection of the epiglottic base as the larynx elevates, whereas epiglottic downward movement to closure is the biomechanical effect of hyolaryngeal movement, downward bolus movement, and tongue base retraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Activation of Kupffer cells on reperfusion following hypoxia: particle phagocytosis in a low-flow, reflow model
Authors: Lindert K. A. , Caldwell-Kenkel J. C. , Nukina S. , Lemasters J. J. , Thurman R. G.
Published: December 2017

Hypoxia is produced selectively in pericentral regions of the liver lobule with a low-flow, reflow perfusion model in which the flow rate is reduced to approximately one-third to one-fourth of normal. This model was used to monitor carbon particle phagocytosis by Kupffer cells during hypoxia and reoxygenation. At normal flow rates, oxygen uptake was 131 mumol.g-1.h-1, pressure was 7.5 cmH2O, and carbon uptake was 150 mg.g-1.h-1. During the low-flow period, oxygen uptake, pressure, and carbon uptake decreased to values of 54 mumol.g-1.h-1, 6.4 cmH2O and 83 mg.g-1.h-1, respectively. Upon reflow, oxygen uptake and pressure increased to 141 mumol.g-1.h-1 and 10.3 cmH2O, respectively. In addition, carbon uptake was elevated approximately threefold to 234 mg.g-1.h-1, indicating activation of Kupffer cells. This activation was prevented by pretreatment with methyl palmitate, a known inhibitor of Kupffer cells. Histological examination revealed significantly more Kupffer cells laden with carbon particles in untreated livers after reflow than in livers from methyl palmitate-treated or untreated rats. Electron microscopic analysis of livers at reflow revealed Kupffer cells with numerous pseudopodia and lamellapodia, reflecting an activated state. These changes were absent in controls or in livers perfused under low-flow conditions. This study demonstrates that Kupffer cells are activated on reoxygenation after hypoxia.
An abnormal rate of actin myosin cross-bridge cycling in colonic smooth muscle associated with experimental colitis
Authors: Xie Y. N. , Gerthoffer W. T. , Reddy S. N. , Cominelli F. , Eysselein V. E. , Snape W. J.
Published: December 2017

Previous studies showed that colonic smooth muscle develops less contractile force to neurohumoral stimulation when associated with mucosal inflammation. This study evaluated 1) the Ca2+ dependence for colonic smooth muscle contraction, 2) the maximum velocity of muscle shortening (Vmax), and 3) changes in 20-kDa myosin light-chain (MLC) phosphorylation in distal circular colonic muscle from healthy rabbits and from rabbits with experimental colitis, induced by Formalin and immune complexes. The isometric tension of unskinned muscle stimulated with bethanechol or KCl was less (P less than 0.05) in animals with colitis compared with the control group. In saponin-skinned muscle, the amplitude of the maximal tension at [Ca2+] of 3 x 10(-7) M was decreased (P less than 0.05) in colitis animals (4.3 +/- 0.9 x 10(4) N/m2, n = 7) compared with healthy animals (10.5 +/- 2.4 x 10(4) N/m2, n = 6). However, the ED50 for Ca2+ stimulation was similar (P greater than 0.05) in both groups. When MLC was thiophosphorylated with ATP gamma S, the tension development was decreased in colitis (2.1 +/- 0.3 x 10(4) N/m2, n = 5; P less than 0.01) compared with normals (5.0 +/- 1.4 x 10(4) N/m2, n = 5). In healthy animals, phosphorylation of 20-kDa MLC increased rapidly to 51.2 +/- 3.1% within 15 s after stimulation and subsequently declined to 19.0 +/- 2.1% at 5 min. Vmax was maximal (0.14 Lo/s) 13 s after stimulation and declined before maximal active isometric stress. In colitis animals, the 20-kDa MLC phosphorylation (P less than 0.05) and the Vmax (P less than 0.01) were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction between carbachol and vasoactive intestinal peptide in cells of isolated colonic crypts
Authors: Greenwald L. , Biagi B. A.
Published: December 2017

In a previous study [B. Biagi, Y.-Z. Wang, and H. J. Cooke, Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G223-G230, 1990], carbachol stimulated active chloride transport in rabbit distal colon, yet had no effect on the basolateral membrane potential (Vbl) of cells from isolated crypts from the same tissue. In the present study, crypt cells were first depolarized with vasoactive intestinal peptide (VIP; 1 x 10(-9) M) (control Vbl = -62 mV; VIP Vbl = -48 mV) and then exposed to carbachol in the presence of VIP. The VIP-induced depolarization of Vbl was completely reversed by carbachol (0.1 mM; repolarization to -65 mV). Similar repolarization was seen by applying carbachol to crypt cells depolarized by 10 mM aminophylline. Intracellular K+ activity (aiK), measured with K(+)-selective microelectrodes, was 64.3 mM (concn = 85 mM), yielding a K+ equilibrium potential (EK+) of -76 mV. Neither carbachol nor VIP application caused significant changes in aiK. These results demonstrate the presence of cholinergic receptors on colonic crypt cells. The magnitude of the carbachol effect on Vbl is greater when Vbl is depolarized relative to EK+. The results are consistent with the hypothesis that carbachol acts by increasing basolateral K+ conductance, driving the cell toward the EK+.
Electric and motor patterns associated with canine jejunal transit of liquids and solids
Authors: Miedema B. W. , Sarr M. G. , Hanson R. B. , Kelly K. A.
Published: December 2017

Our hypothesis was that the direction of liquid transit through the canine jejunum is determined by the direction that single jejunal pressure waves spread, while the direction of solid transit depends on the direction of spread of both single waves and clustered waves. In six dogs, 80-cm jejunal Vella loops were made and fitted with manometric catheters and serosal electrodes. After recovery, transit of liquids (Ringer lactate) and solids (2.4-mm nylon spheres) placed into the center of the loop was determined in the conscious animals while pacing the loop in a forward direction or in a backward direction. Under fasting and fed conditions, single pressure waves followed the direction of pacing, while the direction of migration of clustered waves was not determined by the direction of pacing. Liquid transit always followed the direction of single pressure waves. In contrast, solids moved distally regardless of the direction of pacing, except when liquids were also present in the lumen, in which case solids moved in the same direction as the single pressure waves.
Ascending contraction mediated by 5-hydroxytryptamine3 receptors in canine small intestine
Authors: Mizutani M. , Neya T. , Nakayama S.
Published: December 2017

We investigated the mechanism of ascending contraction induced by activation of 5-hydroxytryptamine3 (5-HT3) receptors in anesthetized dogs. Pressure-measuring balloons were inserted into a loop of extrinsically denervated jejunum. Drugs were administered via the arterial tree to the oral or the anal segment and the ensuing mechanical responses were monitored. Administration of 2-methyl-5-HT (440 pmol-44 nmol) to the anal segment caused contractions in the oral segment in a dose-dependent manner. This response was inhibited by treating the anal segment with ICS 205-930, cocaine, hexamethonium, or tetrodotoxin and by treating the oral segment with atropine or hexamethonium. The response persisted even after abolition of contraction in the anal segment by nifedipine. These results imply that activation of 5-HT3 receptors can induce an ascending contraction through an enteric excitatory pathway formed by a series of cholinergic interneurons and final cholinergic motor neurons, apart from the anal contraction.
Rabbit esophageal cell cytoplasmic pH regulation: role of Na(+)-H+ antiport and Na(+)-dependent HCO3- transport systems
Authors: Layden T. J. , Schmidt L. , Agnone L. , Lisitza P. , Brewer J. , Goldstein J. L.
Published: December 2017

Regulation of cytoplasmic pH (pHi) of esophageal cells assumes importance as these cells can be exposed to mucosally absorbed acid during gastroesophageal reflux episodes. In this study, we examined whether esophageal cells possess pHi transport systems. Esophageal cells were harvested utilizing a gentle trypsin technique that yielded 2-5 x 10(6) cells per esophagus. Cells were attached to a glass cover slip that had been pretreated with rat-tail collagen, and pHi was measured continuously in a spectrofluorometer utilizing 2',7'-bis(2-carboxyethyl)-5(-6)- carboxyfluoroscein acetoxymethyl ester as a pH-sensitive fluorescent probe. The basal pHi of cells exposed to a Na(+)-containing solution averaged 7.52 +/- 0.20 (n = 6). The pHi declined slightly but not significantly to 7.46 +/- 0.12 with the addition of 5% CO2 and 28 mM NaHCO3. When H2 4,4'-diisothiocyanatostilbene- 2,2'-disulfonic acid (DIDS; 0.5 mM) was added, pHi was unchanged. However, addition of 10(-4) M amiloride caused pHi to decrease to 7.29 +/- 0.18 (P less than 0.01). When cells were acidified (pHi 6.3-7.0) using a NH4Cl (20 mM) pulse technique, pHi was rapidly restored toward neutrality in the presence of a HCO3(-)-free external Na+ concentration ([Na+]o)-containing solution (pH units/min = 0.26 +/- 0.12; n = 8). Alkalinization was completely blocked with 10(-4) M amiloride. In the presence of 10(-4) M amiloride, 28 mM NaHCO3, and 5% CO2, acidified cells also alkalinized, although at a slower rate (0.11 +/- 0.04 pH units/min; n = 16).(ABSTRACT TRUNCATED AT 250 WORDS)
Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells
Authors: Chuang C. N. , Tanner M. , Chen M. C. , Davidson S. , Soll A. H.
Published: December 2017

Using enzyme-dispersed canine oxyntic mucosal cells, we studied regulation of histamine release from fractions in which mast cells were largely removed by density gradient. Histamine-like immunoreactivity was demonstrated using peroxidase-anti-peroxidase immunohistochemistry. Histamine-containing cells in the small cell elutriator fractions (SCEF) were further separated by albumin step density gradients. Approximately 2.5% of cells in the low density fraction (LDF) contained histamine-like immunoreactivity; this fraction was largely depleted of the more dense mast cells (0.5%). These two fractions were cultured for 48-64 h on a Matrigel substrate. The cell content of histamine and release into the medium were measured by radioenzymatic assay. Gastrin, carbachol, and forskolin increased histamine release from the LDF. The induction of histamine release by gastrin was evident within 5 min and was sustained for at least 60 min. The response to gastrin was dose dependent between concentrations of 10(-11) and 10(-8) M. In contrast, in the mast cell-enriched SCEF, basal release was higher and gastrin was without effect; however, concanavalin A stimulated and epinephrine inhibited histamine release indicating that histamine-release mechanisms were intact in this fraction. Our methods provide a preparation of low density oxyntic mucosal histamine cells that demonstrate gastrin-responsive histamine release; we speculate that enterochromaffin-like cells account for this gastrin response.
Secretin stimulates bile ductular secretory activity through the cAMP system
Authors: Lenzen R. , Alpini G. , Tavoloni N.
Published: December 2017

Although convincing evidence has been obtained to support a ductular origin of secretin choleresis, the precise mechanism of the choleretic effect of the hormone is poorly understood. The present studies were carried out to 1) further clarify the anatomic site at which secretin stimulates bile flow and 2) establish the signal transduction system underlying this effect. To this end, parenchymal and nonparenchymal liver cells, the latter enriched in bile duct cells, were isolated from rats with ductular cell hyperplasia, and the effect of secretin on intracellular formation of both adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (IPs) was compared with that observed with glucagon and [Tyr10,13,Phe22,Trp25]secretin (SG-secretin). In the pancreas, secretin stimulates both messenger systems, while SG-secretin activates only the cAMP cascade. In isolated hepatocytes, both secretin and SG-secretin failed to increase formation of cAMP and IPs, which were instead activated by glucagon. In isolated bile duct cells, secretin induced formation of both cAMP and IPs, while SG-secretin stimulated solely the cAMP system, as in the pancreas. Glucagon did not stimulate either messenger system in this cell preparation. In vivo, both secretin and SG-secretin stimulated a bicarbonate-rich fluid in rats with bile ductular cell hyperplasia and in normal guinea pigs, which was demonstrated to originate at the distal biliary epithelium. These findings support the existing view that glucagon stimulates canalicular bile flow, while secretin increases secretory activity at the bile ductules and/or ducts. More importantly, they indicate that stimulation of ductular secretory activity by secretin is mediated by the cAMP system and does not involve the IP signal transduction pathway.
Ontogenetic development of nutrient transporters in cat intestine
Authors: Buddington R. K. , Diamond J.
Published: December 2017

Cats are unusual among mammals in several features of nutritional ontogeny related to their strict carnivory as adults. Hence we measured intestinal brush-border uptakes of three sugars and six amino acids, plus intestinal morphometric parameters, in cats from birth until after weaning. The ratio of amino acid to sugar uptake increases with age, in parallel with the increasing protein/carbohydrate ratio of the natural diet. At weaning, when galactose disappears from the natural diet of cats, the galactose/glucose uptake ratio declines steeply, implying a developmental sequence of multiple aldohexose transporters. Fructose uptake remains low at all ages. Uptakes of arginine (hyperessential to cats) and of lysine are notably high throughout the suckling period. The intense perinatal intestinal hyperplasia observed in many other mammal species is absent in cats. The developmental course of intestinal uptake capacities normalized to metabolic live mass parallels the course of relative body growth rates. The "safety margin" of uptake capacity over intake is greater for essential than nonessential amino acids and is greatest for the hyperessential arginine.
Symptomatic responses to stimulation of sensory pathways in the jejunum
Authors: Accarino A. M. , Azpiroz F. , Malagelada J. R.
Published: December 2017

We hypothesized that intestinal afferent pathways inducing perception may be selectively activated by transmucosal electrical nerve stimulation, without disruption of the intrinsic myoelectrical rhythm. Hence, in 12 healthy subjects we measured perception (by a questionnaire) and jejunal slow wave activity (by electromyography), and we randomly applied for 1 min at 5-min intervals graded electrical (15 Hz, 100 microseconds) and mechanical stimuli (balloon distension) in the jejunum up to the respective discomfort threshold. Electrical and mechanical stimuli induced dose-related perception; the perception and discomfort thresholds were 39 +/- 7 and 63 +/- 6 mA and 31 +/- 3 and 49 +/- 5 ml for electrical and mechanical stimuli, respectively. More than one-half of electrical stimuli elicited clinical-type symptoms (abdominal pressure, fullness, colicky or sharp sensation) similar to those induced by mechanical stimuli; the remaining electrical stimuli (38 +/- 10%) induced paresthesia or flutterlike sensation. Similar types of symptoms were perceived with weak and strong stimuli. Jejunal slow wave activity (11.3 +/- 0.4 cycles/min) was not modified by either stimuli. We conclude that activation of intestinal sensory pathways, either by transmucosal nerve stimulation or via mechanoreceptors, induces a similar dose-related symptomatic response, without interfering with the intrinsic myoelectrical activity.
Passive autoregulation of portal venous pressure: distensible hepatic resistance
Authors: Lautt W. W. , Legare D. J.
Published: December 2017

Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined.
Coordination of deglutition and phases of respiration: effect of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease
Authors: Shaker R. , Li Q. , Ren J. , Townsend W. F. , Dodds W. J. , Martin B. J. , Kern M. K. , Rynders A.
Published: December 2017

The effects of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease on the coordination of swallowing with the phases of respiration were studied by concurrent respirography and submental surface electromyography. Study findings showed that in young healthy volunteers, during rest, there is preferential coupling of subconscious swallowing with the expiratory phase of continuous respiration. This preferential coupling of swallowing with expiration was found to increase relative to other phases of respiration during water swallows and tachypnea (P < 0.05). Respiratory phase occurrence of swallowing and postdeglutitive resumption of respiration during exacerbation of chronic obstructive pulmonary disease was found to be significantly different compared with the basal state (P < 0.05). Respiratory phase occurrence of subconscious swallowing in the elderly was found to be different from the young (P < 0.05). Position had no significant effect on the coordination of swallowing and phases of respiration. We concluded that in resting young volunteers the majority of deglutitions are coupled with the expiratory phase of swallowing. This coupling is increased in frequency by the presence of a liquid bolus and tachypnea. And finally, age and chronic obstructive pulmonary disease alter this coordination significantly.
Modulation of cat antral slow waves by ion substitution, Ca2+ and K+ channel blockade, and ACh stimulation
Authors: Renzetti L. M. , Wang M. B. , Ryan J. P.
Published: December 2017

Two distinct slow waves can be recorded from smooth muscle cells on the submucosal border (submucosal cells) and the myenteric border (myenteric cells) in the circular layer of the cat antrum. The present studies examined the effects of decreasing extracellular Na+ ([Na+]o) or Ca2+ concentration ([Ca2+]o), Ca2+ and K+ channel blockade, and acetylcholine (ACh) stimulation on "submucosal" and "myenteric" slow waves using intracellular recording techniques. Decreasing [Na+]o (30 mM) reduced the upstroke depolarization of slow waves from submucosal cells but had no effect on the upstroke depolarization of myenteric cells. Decreasing [Ca2+]o (0.5 mM) decreased the upstroke depolarization in cells from each area. Neither cadmium (200 microM) nor nifedipine (100 microM) had any effect on the upstroke depolarizations from both submucosal and myenteric slow waves. In contrast, nickel (5 mM), a nonselective Ca2+ channel blocker, decreased the upstroke depolarizations of slow waves from submucosal and myenteric cells. Slow waves from myenteric cells normally exhibit a plateau phase of several seconds duration. The amplitude of the plateau potential could be decreased by lowering [Na+]o or [Ca2+]o or by nickel, cadmium or nifedipine. In the presence of 30 mM Na+ slow waves from submucosal cells appeared to develop plateau potentials. K+ channel blockade with tetrabutylammonium (TBA, 5 mM) or cesium (10 mM) increased the upstroke depolarization and delayed membrane repolarization in slow waves from submucosal cells. TBA and cesium also increased the upstroke depolarization from myenteric cells but did not delay membrane repolarization. ACh (1 and 3 microM) caused the generation of plateau potentials in slow waves from submucosal cells and increased slow-wave duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential effects of ATP-MgCl2 on portal and hepatic arterial blood flow after hemorrhage and resuscitation
Authors: Wang P. , Ba Z. F. , Chaudry I. H.
Published: December 2017

Although ATP-MgCl2 administration after hemorrhage and resuscitation restores the decreased hepatic blood flow, it is not known whether this is due to the increase in portal blood flow or hepatic arterial blood flow. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal shed blood volume was returned in the form of Ringer lactate (RL). The animals were resuscitated with four times the volume of the shed blood with RL, during and after which ATP-MgCl2 (50 mumol/kg body wt) or an equal volume of normal saline was infused intravenously over 95 min. Cardiac output and organ blood flow were determined by 85Sr-labeled microspheres at 90 min after the completion of resuscitation. The results indicate that portal blood flow and total hepatic blood flow decreased significantly after hemorrhage and resuscitation. ATP-MgCl2 treatment, however, restored these parameters to sham values. In contrast, hepatic arterial blood flow did not change significantly after either hemorrhage and resuscitation or ATP-MgCl2 infusion. Moreover, the depressed cardiac output was normalized and coronary blood flow was higher than shams after ATP-MgCl2 treatment. Unlike small intestinal blood flow, blood flows to the stomach, spleen, pancreas, mesentery, and cecum were not markedly affected with ATP-MgCl2 infusion. Thus the restoration of hepatic blood flow with ATP-MgCl2 treatment under such conditions is due to the increased portal blood flow, i.e., solely due to the increased small intestinal blood flow.