bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholecystokinin-induced formation of inositol phosphates in pancreatic acini
Authors: Rowley W. H. , Sato S. , Huang S. C. , Collado-Escobar D. M. , Beaven M. A. , Wang L. H. , Martinez J. , Gardner J. D. , Jensen R. T.
Published: December 2017

For cholecystokinin (CCK) and the partial agonist CCK-JMV-180 [Boc-Nle28,31,CCK-(27-32)-2-phenylethyl ester], we examined their abilities to stimulate the accumulation of inositol phosphates (IP), mobilize intracellular calcium, and stimulate enzyme secretion in rat pancreatic acini. CCK-8 caused an increase in [3H]IP2 and [3H]IP3 at 10 s and a slower increase in [3H]IP1. High-pressure liquid chromatography separation demonstrated that at 10 s 100% of the increase of [3H]IP3 was IP3(1,4,5). CCK-JMV-180 caused no increase in [3H]IP3 at 10 s and only 28% of the maximal increase seen with CCK-8 at 15 min. CCK-8 caused an 11-fold increase in calcium outflux, whereas CCK-JMV-180 was only 45% as effective and 3,000 times less potent. CCK-JMV-180 antagonized the CCK-8-stimulated increase in [3H]IP3 and mobilization of intracellular calcium. CCK-8 caused an 81-fold increase at 2.5 s in IP3(1,4,5) measured by a mass radioreceptor assay and half-maximal stimulation occurred at 2 nM, whereas CCK-JMV-180 only caused a 3-fold increase. Analysis of the ability of CCK-8 or CCK-JMV-180 to stimulate enzyme secretion demonstrated that at low concentrations, each peptide stimulates enzyme secretion without causing detectable calcium mobilization, whereas at increasing peptide concentrations calcium mobilization occurs without detectable accumulation of IP3(1,4,5), but at still higher concentrations IP3(1,4,5) accumulation is finally detected. These results demonstrate that peptides that stimulate enzyme secretion by interacting with CCK receptors can cause maximal stimulation with minimal changes in calcium mobilization and maximal changes in calcium mobilization occur with minimal changes in IP3(1,4,5), suggesting marked amplification.
Effect of duodenal amino acid infusion on solid gastric emptying in pigs
Authors: Landers B. R. , Devitt P. G. , Jamieson G. G.
Published: December 2017

The emptying of a 400-g test meal of cubed liver was studied in eight pigs equipped with duodenal cannulas. Gastric effluent was diverted to measure both the rate of emptying and the distribution of particle sizes. The effect of emptying and particle size of infusing normal saline or an isosmolar amino acid solution into the small bowel was studied. Normal saline infusion did not alter the proportion of particles emptied, which were less than 1 mm in diameter. Infusion of the amino acid solution at the same rate significantly decreased the mass of liver emptied from 69.9 to 38.4 g compared with normal saline, and the percentage of particles less than 1 mm in diameter in the gastric effluent increased from 66 to 82%. We conclude that the amino acid solution produced both a reduction in the rate of gastric emptying and an increase in the proportion of small particles in the gastric effluent. We postulate that this may have been due to changes in gastric motility, together with alterations in gastric secretion and digestion, produced by the infusion of the amino acid solution into the small bowel.
Fat feeding increases size, but not number, of chylomicrons produced by small intestine
Authors: Hayashi H. , Fujimoto K. , Cardelli J. A. , Nutting D. F. , Bergstedt S. , Tso P.
Published: December 2017

To test the regulatory effect of dietary triglyceride (TG) on rat lymphatic apolipoprotein B (apo B) transport, lymph-fistula rats were infused intraduodenally for 8 h at 3 ml/h with a lipid emulsion containing 40 mumol TG labeled with glycerol [9,10-3H(N)]triolein, 7.8 mumol egg phosphatidylcholine, and 57 mumol sodium taurocholate in phosphate-buffered saline with or without 1 mg/h Pluronic L81 (L81). L81 is known to prevent lipid transport in the intestine by inhibiting the formation of chylomicrons (CM). This action of L81 is quickly reversible by merely replacing L81 infusion by saline infusion. In the control rats (without L81 added to the infusate), the amount of apo B secreted in either whole lymph, CM, or the very-low-density lipoprotein (VLDL) fractions did not change significantly during lipid infusion compared with fasting. Compared with the fasting, the apo B output in lymph during L81 plus lipid or saline infusion in the experimental rats did not change significantly. The lymphatic apo B output data were also supported by the incorporation studies using [3H]leucine. In summary, these data demonstrate that the absorption of a physiological load of lipid into lymph does not affect the apo B synthesis in the mucosa or the secretion of apo B in lymph. Furthermore, the action of L81 is probably not by inhibiting intestinal apo B production because apo B secretion was not affected by the presence of L81. This study also demonstrates that the number of CM particles made by the small intestine remains relatively constant during fasting or active lipid uptake and transport. During active lipid absorption, instead of increasing the number of CM, the enterocytes expand the size of the CM particles. Lastly, the number and TG content of VLDL particles synthesized and secreted by the small intestine also seems to remain relatively constant during fasting and active lipid absorption.
Phagocytosis by Kupffer cells predominates in pericentral regions of the liver lobule
Authors: te Koppele J. M. , Thurman R. G.
Published: December 2017

These studies were designed to determine whether particle phagocytosis could be monitored from the surface of the perfused liver. To achieve this goal, decreases in reflected light were measured during phagocytosis of colloidal carbon particles. Livers were illuminated with 623-nm light via a relatively large fiber-optic light guide (tip diam 2 mm), and reflected light was monitored continuously. A decrease in reflected light was observed when carbon was infused that was proportional to the influent carbon concentration. Initial changes in reflected light were linearly related to rates of carbon uptake by Kupffer cells. Subsequently, rates of carbon uptake were determined from changes in reflected light in periportal and pericentral regions of the liver lobule with miniature fiber-optic light guides. In perfusions in the anterograde direction, rates of carbon uptake were approximately 80% higher in pericentral than periportal regions of the liver lobule. This pattern was reversed when livers were perfused in the retrograde direction. Thus particle phagocytosis predominates in downstream regions of the liver lobule. Because decreasing the pH of the influent perfusate increased carbon uptake, the pH gradient over the liver lobule may be involved in the regulation of particle uptake at the sublobular level.
Luminal glucose concentrations in the gut under normal conditions
Authors: Ferraris R. P. , Yasharpour S. , Lloyd K. C. , Mirzayan R. , Diamond J. M.
Published: December 2017

Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.
Modulation of submucosal cholinergic neurons by 5-hydroxytryptamine and neuropeptides
Authors: Yau W. M. , Dorsett J. A. , Youther M. L.
Published: December 2017

Release of [3H]acetylcholine ([3H]ACh) was examined in a submucous plexus preparation obtained from the guinea pig small intestine in vitro. Constant-current field stimulation evoked ACh output; this output was dependent on the stimulus frequency applied. Maximal release was observed at 10 Hz; this release was blocked by tetrodotoxin (1 x 10(-6) M) or in Ca2(+)-free buffer. Serotonin [5-hydroxytryptamine (5-HT)] stimulated the release of ACh dose dependently, with an ED50 of 5 x 10(-7) M. Substance P was ineffective, while vasoactive intestinal peptide weakly stimulated ACh secretion. Several neuropeptides were tested on their ability to modulate 5-HT-evoked ACh release. Dynorphin A inhibited 5-HT-stimulated ACh release, while Met-enkephalin was without any effect. Both somatostatin and galanin were effective modulators, with an inhibitory effect in the submicromolar range and an excitatory effect at higher concentrations. The response characteristics of the cholinergic neurons of submucosal plexus differ markedly from those of the myenteric plexus. These distinct features form an important framework for future functional studies on submucous plexus neurons.
Characterization of the opioid receptor type mediating inhibition of rat gastric somatostatin secretion
Authors: McIntosh C. H. , Jia X. , Kowk Y. N.
Published: December 2017

The opioid peptides are potent inhibitors of gastric somatostatin-like immunoreactivity (SLI) secretion from the isolated perfused rat stomach. In addition, inhibition of SLI secretion induced by vagal stimulation is partially blocked by naloxone, indicating that endogenously released opioid peptides probably play a physiological role in the regulation of SLI release. The opioid peptides exert their effects by interacting with a number of different receptor types. In the present study, the effect of the selective delta-opioid receptor agonists [D-Pen2.5]enkephalin and [D-Pen2,L-Pen5]enkephalin and the mu-receptor agonist [D-Ala2, N-methyl (NMe)-Phe4,Gly5-ol]enkephalin on gastric inhibitory polypeptide (GIP)-stimulated SLI secretion from the isolated perfused rat stomach have been studied. Responses to the less selective delta-agonist [D-Ala2,D-Leu5]enkephalin, dynorphins 1-8, 1-13, and 1-17, and the extended enkephalin forms Met-enkephalin-Arg6-Phe7,Met- enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Arg7-Val8-NH2 (metorphamide), have also been investigated. [D-Ala2,NMe-Phe4,Gly5-ol]enkephalin induced a concentration-dependent inhibition of GIP-stimulated SLI secretion, with 50% of maximal inhibition at 10 nM. Neither [D-Pen2.5]enkephalin nor [D-Pen2,L-Pen6]enkephalin (10 nM to 1 microM) had any effect on SLI release, and [D-Ala2,D-Leu5] enkephalin inhibited SLI release only at high concentrations. Met-enkephalin-Arg6-Phe7 and metorphamide both inhibited SLI release, whereas Met-enkephalin-Arg6-Gly7-Leu8 and the dynorphins had little or no effect. In conclusion, the strong inhibition of SLI secretion produced by [D-Ala2,NMe-Phe4,Gly5-ol] enkephalin and lack of major effect of [D-Pen2.5]-enkephalin, [D-Pen2,L-Pen5]enkephalin, and the dynorphins indicate that opioid peptide-induced inhibition was mediated by interaction with mu-receptors and that neither delta or kappa-receptors play a significant role.
Chemotactic peptide effects on intestinal electrolyte transport
Authors: Barrett T. A. , Musch M. W. , Chang E. B.
Published: December 2017

The bacterial-derived chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) increases short-circuit current (Isc) and arachidonic acid metabolism (AAM) in rabbit ileum and distal colon. Serosal (s) or mucosal (m) addition of fMLP transiently increases Isc. Half-maximally effective dose and maximal increases in Isc were 32 nM and 84 microA/cm2 in ileum and 234 nM and 80 microA/cm2 in colon, respectively. Piroxicam, a cyclooxygenase inhibitor, diminished the Isc response by 97% in colon and 69% in ileum. Changes in Isc were dependent on Cl- and HCO3- in the bathing media. In ileum, fMLP inhibited m-to-s 36Cl- fluxes and stimulated s-to-m 36Cl- fluxes. These changes in Cl- flux were also inhibited by piroxicam. fMLP stimulated prostaglandin E2 (PGE2) release in intact tissue and in isolated subepithelial components. Increased tissue adenosine 3',5'-cyclic monophosphate levels were detected in intact tissue but not in isolated components. Previous desensitization of ileum to PGE1 inhibited fMLP stimulation of Isc in ileum by 88%. Desensitization to fMLP in ileum failed to alter the effect of PGE1 (10 microM) on Isc. In isolated microsomal membranes of ileal enterocytes, fMLP binding sites could not be demonstrated, suggesting that fMLPs action was initially mediated via stimulation of nonepithelial cell cyclooxygenase activity. The above results indicate that fMLP stimulates net secretion in both ileum and colon probably by the activation of AAM.
Cerebral potentials evoked by esophageal distension in human
Authors: Smout A. J. , DeVore M. S. , Castell D. O.
Published: December 2017

Recent studies have shown that cerebral evoked potentials (EPs) can be recorded after balloon distension of the human esophagus. The aim of this study was to evaluate the characteristics of these viscerosensory EPs and to investigate the relations between these EPs and perception of esophageal distension. Nineteen healthy volunteers (22-60 yr old) were studied. A balloon positioned 5 cm above the lower esophageal sphincter was inflated 10 times each minute. EPs recorded from four midline scalp electrodes were averaged for 50 and 100 inflation cycles. A clearly defined triphasic (negative-positive-negative) EP was recorded in all subjects and from all four recording sites when a volume leading to definite sensation and rapid balloon inflation (170 ml/s) was used. The latencies of the peaks were 231 +/- 7 (N1), 303 +/- 7 (P1), and 379 +/- 8 ms (N2). No significant correlation between stimulus perception and latency was found. The amplitude and quality of the EPs (scored by 3 blinded observers) increased significantly (P less than 0.01, ANOVA) with increasing sensation. Slow balloon inflation (30 ml/s) was significantly less effective in evoking EPs than rapid inflation (P less than 0.01). The EPs evoked by 100 inflations were not significantly clearer than those evoked by 50 inflations. It is concluded that the ability to record cerebral potentials evoked by esophageal balloon distension is related to the rate of balloon inflation and to the level of awareness of the stimulus.
Hormonal mechanism of sodium oleate-stimulated pancreatic secretion in rats
Authors: Li P. , Lee K. Y. , Chang T. M. , Chey W. Y.
Published: December 2017

We have investigated the role of two intestinal hormones, secretin and cholecystokinin (CCK), on the pancreatic exocrine secretion stimulated by sodium oleate in anesthetized rats. Each rat was prepared with a polyethylene tube in the proximal duodenum and ligation of the pylorus. To collect pancreatic juice, the common bile-pancreatic duct was cannulated near the duodenal wall while bile was diverted to the exterior. Intraduodenal infusion of sodium oleate at doses of 0.03, 0.06, 0.12, and 0.24 mmol/h resulted in significant increases in pancreatic secretion including fluid, bicarbonate, and protein output. The increases of the three parameters were dose dependent and were correlated well with the increases in plasma secretin and CCK concentrations. To further clarify their hormonal roles, we have repeated identical experiments under intravenous administration of a rabbit anti-secretin serum (0.1 ml) or CR 1409 (4 mg.kg-1.h-1), a CCK-receptor antagonist, or a combination of both the antiserum and CR 1409. The antiserum significantly suppressed volume flow and bicarbonate secretion with a minor inhibitory effect on protein secretion, whereas a normal rabbit serum did not. CR 1409 significantly suppressed all three parameters. The combined treatment with both the antiserum and CR 1409 almost completely abolished the pancreatic secretion. Atropine given intravenously significantly inhibited the protein output but did not influence volume flow or bicarbonate output in response to sodium oleate. We thus conclude that, in rats, fat-stimulated pancreatic secretion of volume flow and bicarbonate depends entirely on the circulating endogenous secretin and CCK but that the protein output appears to be under control of both hormonal and cholinergic controls.
Function of rat hepatocyte tight junctions: studies with bile acid infusions
Authors: Hardison W. G. , Dalle-Molle E. , Gosink E. , Lowe P. J. , Steinbach J. H. , Yamaguchi Y.
Published: December 2017

To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin
Authors: Xing L. P. , Balaban C. , Seaton J. , Washington J. , Kauffman G.
Published: December 2017

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.
Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats
Authors: White R. L. , Rossiter C. D. , Hornby P. J. , Harmon J. W. , Kasbekar D. K. , Gillis R. A.
Published: December 2017

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
PACAP and VIP receptors in rat liver membranes
Authors: Robberecht P. , Gourlet P. , Cauvin A. , Buscail L. , De Neef P. , Arimura A. , Christophe J.
Published: December 2017

Pituitary adenylate cyclase activating peptide (PACAP) tested as PACAP-(1-38)NH2 and PACAP-(1-27)NH2 and vasoactive intestinal polypeptide (VIP) were compared for their capacity to discriminate between high- and low-affinity VIP-preferring receptors that coexist in rat liver plasma membranes. This capacity was evaluated by the ability to 1) inhibit 125I-labeled-PACAP-(1-27)NH2, 125I-labeled-VIP, and 125I-labeled-helodermin binding and 2) to activate adenylate cyclase. PACAP-(1-27)NH2 bound specifically and reversibly to three classes of binding sites, as revealed by analysis of binding curves. On high-affinity VIP receptors (tested specifically by [125I]-helodermin binding), PACAP-(1-38)NH2 showed lower affinity than PACAP-(1-27)NH2 and VIP itself. On low-affinity VIP receptors, PACAP-(1-27)NH2 and -(1-38)NH2 showed similar modest affinity that was slightly higher however than that of VIP. For a third specific class of PACAP receptors (20% of PACAP receptors not recognized by VIP), PACAP-(1-38)NH2 showed higher affinity than PACAP-(1-27)NH2. Both PACAPs stimulated rat liver adenylate cyclase with the same low efficacy as VIP but with an affinity even greater [half-maximal effective concentration (EC50) 0.02 nM] than that of VIP (EC50 0.05 nM).
Index of contractility: quantitative analysis of hepatic venous distensibility
Authors: Lautt W. W. , Greenway C. V. , Legare D. J.
Published: December 2017

The low-pressure resistance vessels of the splanchnic circulation are passively distensible, and changes in regional blood pressures can lead to large changes in vascular resistance. The relationship between distending blood pressure (Pd) and vascular resistance (R) is described as a constant, the index of contractility (IC) where IC = R x Pd3. IC was derived in an isolated blood-perfused liver and was confirmed in vivo for both pre- and postsinusoidal resistance sites. IC does not change passively in response to wide changes in blood flow or hepatic outflow pressure. IC is dramatically altered in response to active vasoconstriction. In vivo, the presinusoidal IC rose from a control level of 12.2 +/- 4.2 to 92.7 +/- 20.6 IC units (mmHg4.ml-1.min.kg body wt) in response to 1.25 micrograms.kg-1.min-1 norepinephrine intraportal; the postsinusoidal IC rose from 20.4 +/- 2.3 to 59.6 +/- 14.2 IC units. IC reflects resistance changes secondary to active contractile responses independent of the passive consequences of the distensible nature of the resistance sites. We suggest that these concepts can be applied to any vascular bed with distensible resistance vessels.
Sensory neurons mediate protective vasodilatation in rat gastric mucosa
Authors: Holzer P. , Livingston E. H. , Saria A. , Guth P. H.
Published: December 2017

Sensory nerve stimulation by intragastric capsaicin (160 microM) prevents ethanol injury to the gastric mucosa and facilitates gastric mucosal blood flow (GMBF). The present study examined whether the capsaicin-induced increase in GMBF accounts for mucosal protection. Gastric perfusion of capsaicin (160 microM) in urethan-anesthetized rats did not change blood pressure but significantly enhanced GMBF as measured by hydrogen gas clearance. The same increase in GMBF was seen when capsaicin was administered together with an injurious concentration of ethanol (25%). GMBF was facilitated by capsaicin in a dose-related manner (10-640 microM), and the dose-dependent vasodilatation was significantly correlated with a dose-dependent reduction of gross damage to the mucosa. Histology showed that capsaicin prevented deep but not superficial mucosal damage. The vasodilator and protective effects of capsaicin resulted from stimulation of sensory neurons and propagation of nerve activity, since they were blocked after ablation of capsaicin-sensitive neurons or local intra-arterial infusion of tetrodotoxin. This and the finding of a limited access of intragastric capsaicin to the gastric wall indicates that the vasodilator and protective effects of capsaicin are mediated by a neural reflex. It is concluded that facilitation of GMBF is the major mechanism of sensory nerve-mediated prevention of gastric mucosal injury.
Characteristics of luminal bicarbonate secretion by rat cecum in vitro
Authors: Canfield P.
Published: December 2017

Under in vitro conditions the rat cecum transported HCO3- from the serosal to an unbuffered solution in contact with the mucosal side [Js----m = 7.12 +/- 0.18 mumol.cm-2.h-1 (n = 149)]. With reversed tissues, a significantly lower flux was obtained [Jm----s = 2.47 +/- 0.11 mumol.cm-2.h-1 (n = 42)]. Both fluxes were stable for several hours. Increasing the H+ gradient across the tissue for 60 min did not change either flux. Anoxia for 45 min reversibly reduced Js----m by 65 +/- 3% (n = 20) but had no effect on Jm----s. Both fluxes were linearly related to HCO3- concentration on the buffered side, but the slope for Js----m was 3.5 times that for Jm----s. When tissues were initially set up in HEPES buffer rather than HCO3-, Js----m was 0.12 +/- 0.05 mumol.cm-2.h-1 (n = 6), which is not significantly different from zero. Replacement of Na+ by choline reduced Js----m by 40 +/- 3% (n = 11) and ouabain (1 mM) by 24 +/- 3% (n = 5). Replacement of Cl- with isethionate or K+ with Na+ for 60 min did not alter Js----m. Serosal application of DIDS (0.5 mM) reduced Js----m by 24 +/- 6% (n = 6), but SITS (0.5 mM), furosemide (1 mM), acetazolamide (0.1 mM), amiloride (1 mM), and a proton pump inhibitor (Sch 28080, 50 microM) had no effect. Mucosal application of DIDS, furosemide, and amiloride had no effect on Js----m. Serosal tetrodotoxin (1 microM) and indomethacin (28 microM) were also without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Strong gastric contractions cause mucosal ischemia
Authors: Livingston E. H. , Howard T. J. , Garrick T. R. , Passaro E. P. , Guth P. H.
Published: December 2017

Contractions of a segment of bowel result in alterations of its blood flow. However, the precise temporal and spacial relationships between contractions and mucosal blood flow are unknown. Rats were fitted with strain gauge force transducers and implanted with silver wire electrodes into the muscularis externa of the stomach. In vivo microscopic observation of motility and of the gastric mucosal blood flow was performed during electrical field-stimulated contractions. Contractions originated in the midcorpus, were 0.237 +/- 0.018 cm wide, traveled along the corpus at 0.133 +/- 0.024 cm/s, and had a duration of 5.9 +/- 0.1 s. Antral contractions were 0.174 +/- 0.032 cm wide, traveled at 0.070 +/- 0.009 cm/s, and had a duration of 5.6 +/- 0.7 s. During the contraction, capillary flow velocity in the corpus decreased from a basal value of 410 +/- 105 to 206 +/- 104 microns/s at the peak of a contraction. Five seconds after the contraction was released hyperemia was observed with the flow velocity increasing to 570 +/- 102 microns/s. In the antrum, flow stopped completely during the contraction irrespective of the initial flow velocity and no hyperemia occurred with release of the contraction; rather, flow velocity slowly returned to baseline values. In both regions the flow reductions were in phase with the contractions as measured by the force transducers. These studies provide direct evidence that strong gastric contractions can effectively reduce or stop gastric mucosal blood flow.
Excitatory and inhibitory responses of Oddi's sphincter in guinea pigs
Authors: Hirose T. , Ito Y.
Published: December 2017

We examined the intrinsic motor innervation of the guinea pig choledochoduodenal junction and actions of cholecystokinin octapeptide (CCK-OP) on contractile and membrane activity of circular and longitudinal smooth muscles from three different areas: close to the choledochal sphincter (I); central area in the ampulla (II); and close to the duodenal papilla (III). In response to electrical field stimulation, circular muscle strips showed an initial twitchlike contraction followed by relaxation in areas I and II and only a transient relaxation in the muscle strips prepared from area III. In the longitudinal strips, the regional differences in response to the field stimulation were not prominent, and biphasic twitchlike contractions were observed in areas I, II, and III. Electric field stimulation evoked excitatory junction potentials (EJPs), inhibitory junction potentials (IJPs), or biphasic membrane response (initial EJP followed by an IJP) in the circular and longitudinal smooth muscle cells. Prominent regional differences were observed in areas I, II, and III. Namely, in area III both the circular and longitudinal muscle layers IJPs predominated, whereas in area I the response was predominantly excitatory. CCK-OP (greater than 10-8M) evoked repetitive action potentials in the circular muscle cells, and CCK-OP increased the frequency of slow waves or the spontaneous action potentials in longitudinal muscle cells. CCK-OP enhanced the amplitude of the IJPs and EJPs in both muscle layers. It would thus appear that bile flow is controlled by complex combinations of contraction and relaxation of the smooth muscle that may be due to regional differences in excitatory and inhibitory innervations.
Avian cecum: role of glucose and volatile fatty acids in transepithelial ion transport
Authors: Grubb B. R.
Published: December 2017

In the fowl cecum in vitro, the influence of glucose and the three most prevalent naturally occurring volatile fatty acids (acetate, propionate, butyrate) on short-circuit current (Isc), electrical resistance, and transport of Na and Cl was determined. When glucose, acetate, or butyrate was present, ion transport was characterized by electrogenic Na absorption, greater than 65% of which was amiloride inhibitable, and Cl secretion, which also was electrogenic. Isc could be completely accounted for by net fluxes of Na and Cl. When glucose, acetate, or butyrate (10 mM both sides) was included in the incubation medium, cecal tissue maintained its Isc and a constant rate of net Na absorption and Cl secretion for a 5-h period. When no substrate was present or propionate was included in the medium, a marked fall in Isc and net Na and Cl fluxes was seen. Glucose caused an increase in Isc when added only to the serosal side. As 3-O-methylglucose (not metabolized) was not effective in stimulating Isc of the cecum (serosal or mucosal addition), it appeared that glucose increased Isc by acting as an energy substrate for active Na transport. Acetate and butyrate appeared to be equally effective in stimulating Na transport and Isc when placed on either side of the membrane. When the preparation was supplied with glucose (serosal side) and acetate was added to the mucosal side, no further stimulation of Isc occurred. Thus it appeared that acetate and butyrate were acting as substrates for active Na transport rather than stimulating Na transport by some other mechanism such as a cotransport with Na.(ABSTRACT TRUNCATED AT 250 WORDS)
Videoradiographic, manometric, and electromyographic analysis of canine upper esophageal sphincter
Authors: Lang I. M. , Dantas R. O. , Cook I. J. , Dodds W. J.
Published: December 2017

We assessed upper esophageal sphincter (UES) function in dogs by concurrent recording of cricopharyngeal electromyographic (EMG) activity, intraluminal pressure, and dimensional changes of the pharyngoesophageal junction at rest and during swallowing. Radial and axial pressure profiles of the UES were determined by continuous pull-through manometry. EMG activity of the cricopharyngeus and thyropharyngeus muscles were correlated with UES pressure under static conditions. We also quantified the temporal relationships among EMG activity of the cricopharyngeus, UES pressure, and pharyngoesophageal junction dimensional changes during swallowing of 2, 4, and 6 ml of barium. When the dogs were prone, the anterior and posterior UES pressures were about twice the lateral pressures and the axial length of the UES was approximately 4 cm. All radial pressures equalized to approximately 20 mmHg when the dogs lay on their sides. The peak pressure zone of the UES corresponded closely with the level of the cricopharyngeal electrode, and resting UES pressure correlated closely with cricopharyngeal but not thyropharyngeal EMG activity. During swallowing, the cricopharyngeus relaxed approximately 200 ms before UES opening and 100 ms before UES relaxation. Superior movement of the hyoid and the larynx was associated temporally with UES relaxation, while anterior movement was associated with UES opening. Increases in bolus volume significantly increased maximal sagittal UES diameter during UES opening but did not alter temporal changes in UES function.(ABSTRACT TRUNCATED AT 250 WORDS)
Vagal stimulation-induced gastric damage in rats
Authors: Hierlihy L. E. , Wallace J. L. , Ferguson A. V.
Published: December 2017

The role of the vagus nerve in the development of gastric mucosal damage was examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation was applied to the vagus nerves for a period of 60 min, after which macroscopic gastric damage was scored and samples of the stomach were fixed for later histological assessment. Damage scores were assigned blindly based on a 0 (normal) to 3 (severe) scale. Stimulation of vagal afferents or efferents in isolation did not result in significant damage to the gastric mucosa (P greater than 0.1). In contrast, stimulation of both intact vagus nerves resulted in significant gastric mucosal damage (mean damage score, 2.0 +/- 0.33, P less than 0.01). A second series of experiments demonstrated this gastric damage to be induced within 30-60 min; extending the stimulation period to 120 min did not worsen the gastric damage scores significantly (P greater than 0.1). In a third study, stimulation of both intact vagus nerves after paraventricular nucleus (PVN) lesion resulted in damage scores (0.33 +/- 0.17) that were significantly reduced compared with intact PVN and non-PVN-lesioned animals (P less than 0.01). These results indicate that the development of vagal stimulation-induced gastric damage requires the activation of both afferent and efferent vagal components and suggest further that such damage is dependent upon an intact PVN.
Radiation and indomethacin effects on morphology, prostaglandins, and motility in dog jejunum
Authors: Summers R. W. , Glenn C. E. , Flatt A. J. , Elahmady A.
Published: December 2017

Irradiation can have a profound effect on intestinal motor activity. Previous studies have suggested that prostaglandins may play some role in radiation-induced enteritis. The present study investigated the effects of abdominal X-irradiation with or without indomethacin treatment on jejunal myoelectric activity and prostaglandin synthesis by measuring the prostaglandin content of mesenteric arterial and venous plasma and in the intestinal lumen in dogs. After X-irradiation, venous concentrations and arteriovenous concentration differences of prostaglandin (PG)E2, PGF2 alpha, and 6-keto-PGF1 alpha increased markedly. The increased venous concentrations were in part attributable to increased mucosal and/or submucosal synthesis by inference from increased concentrations of these metabolites assayed from the jejunal lumen. Irradiation produced histological damage to the mucosa and submucosa and abnormalities in the migrating motor complex, jejunal slow waves, and a decrease in spike burst activity. Inhibition of prostaglandin synthesis by treating the animals with indomethacin reduced the severity of illness, the histological injury, and changes in myoelectric activity induced by irradiation. Such treatment should be evaluated further to treat patients exposed to large doses of irradiation.
Electrical slow-wave activity from the circular layer of cat terminal antrum
Authors: Renzetti L. M. , Wang M. B. , Ryan J. P.
Published: December 2017

Intracellular recording techniques were used to characterize the electrical slow-wave activity through the thickness of the circular muscle layer of the cat terminal antrum. Muscle strips were pinned out in cross section to the floor of a recording chamber perfused with Krebs buffer. Circular muscle cells from the myenteric to the submucosal border then were impaled with 20- to 40-M omega glass microelectrodes, and slow-wave activity was recorded. Slow waves from the myenteric side of the circular layer consisted of an upstroke depolarization, a prominent plateau phase, and a downstroke repolarization. Slow-wave characteristics for cells along the myenteric border were Em, -74.2 +/- 1.3 mV; duration, 5.3 +/- 0.5 s; upstroke amplitude, 29.4 +/- 3.4 mV; upstroke velocity, 0.20 +/- 0.03 V/s; and frequency, 5.8 +/- 0.5/min. Slow waves from muscle cells along the submucosal side of the preparation lacked a discernible plateau phase. Slow waves from submucosal border cells had the following characteristics: Em, -80.4 +/- 1.4 mV (P less than 0.01); duration, 3.5 +/- 0.4 s (P less than 0.01); upstroke amplitude, 44.0 +/- 2.4 mV (P less than 0.01); upstroke velocity, 0.56 +/- 0.06 V/s (P less than 0.01); and frequency, 4.2 +/- 0.4/min (P less than 0.05). Slow waves were not affected by 10(-7)M tetrodotoxin and 10(-6)M atropine or by removal of the longitudinal muscle layer. Slow-wave activity within each region was maintained after dissecting the circular layer into submucosal and myenteric segments. The results suggest that two distinct slow waves exist within the circular muscle layer of the cat terminal antrum.(ABSTRACT TRUNCATED AT 250 WORDS)
Method for prolonged ambulatory monitoring of high-amplitude propagated contractions from colon
Authors: Crowell M. D. , Bassotti G. , Cheskin L. J. , Schuster M. M. , Whitehead W. E.
Published: December 2017

This study monitored high-amplitude propagated contractions (HAPCs) in ambulating subjects over a 24-h period using a new ambulatory recording system. Twelve healthy volunteers aged 34 +/- 5.96 yr participated. Approximately 12 h after a Colyte bowel prep, a small catheter (OD less than 3 mm), containing three solid-state pressure transducers spaced 5 cm apart, was positioned by flexible sigmoidoscope at 40-50 cm from the anal verge. A battery-operated data recorder sampled the pressure at each port at 1 Hz and stored the values on all ports if any port exceeded 75 mmHg. At the conclusion of the 24-h period, an X-ray was taken to confirm the location of the catheter. Fifty-four percent of all HAPCs preceded a bowel movement by less than or equal to 1 h. Forty-nine percent of all HAPCs occurred within 1 h after a high-fat meal, and 33% occurred within 1 h of morning awakening. Reverse propagated waves, not previously described in the colon, were observed in three individuals. Spontaneous high-amplitude caudally propagated contractions occur 6.9 +/- 1.5 times/24 h in the sigmoid colon in ambulating asymptomatic individuals and are temporally related to defecation and meals. Peristaltic activity is decreased during sleep. This recording technique was reliable and well tolerated in all participants.
Use of the ileal conduit as a model for studying human small intestinal mucus glycoprotein secretion
Authors: Roberton A. M. , Rabel B. , Harding C. A. , Tasman-Jones C. , Harris P. J. , Lee S. P.
Published: December 2017

To establish a human model system for investigating control of mucus secretion by the small intestine, we have studied the output of mucus glycoprotein in the urine of patients with ileal conduits. A highly specific enzyme-linked immunosorbent assay (ELISA) was used to measure mucus glycoprotein with a sensitivity down to 0.3 ng protein of mucus glycoprotein. The assay detects human ileal mucus glycoprotein in the urine of ileal conduit patients; for an individual subject, the amount hardly varied from day to day, although there were substantial differences between individuals in the amounts secreted. Control urine from persons with normal bladders did not contain any mucus glycoprotein that reacted in the ELISA. The model has many advantages over other experimental systems for studying the rate of mucus glycoprotein secretion from the human ileum and can also be used as a reproducible resource of undegraded mucus glycoprotein.
Profound increase in viscosity and aggregation of pig gastric mucin at low pH
Authors: Bhaskar K. R. , Gong D. H. , Bansil R. , Pajevic S. , Hamilton J. A. , Turner B. S. , LaMont J. T.
Published: December 2017

Epithelial mucins are glycoproteins of very large molecular weight that provide viscoelastic and gel-forming properties to mucus, the jellylike protective layer covering epithelial organs. In the mammalian stomach the mucus gel layer protects the underlying epithelial cells from HCl in the lumen. We report here that pig gastric mucin undergoes a 100-fold increase in viscosity in vitro when pH is lowered from 7 to 2. Sedimentation velocity and dynamic light-scattering measurements revealed the formation of extremely large aggregates at low pH consistent with the observed increase in viscosity. Aggregation of mucin at low pH was prevented by increasing the ionic strength, suggesting the involvement of electrostatic interactions. Trypsin digestion and thiol reduction, but not enzymatic removal of neuraminic acid, prevented aggregation at low pH. This implies that the peptide core rather than the oligosaccharide side chains of the molecule is involved in the aggregation of mucin at low pH. Increased aggregation and viscosity at low pH were also observed in a solvent made to mimic the ionic composition of gastric juice, indicating the physiological relevance of our findings. Our observations suggest that one mechanism of gastric protection may be the ability of gastric mucin to undergo aggregation with a marked increase in viscosity at low pH.
Mechanism of aggravation of mucosal injury by intravenous nicotine in rat stomach
Authors: Endoh K. , Kauffman G. L. , Leung F. W.
Published: December 2017

Endogenous prostaglandins and injury-induced hyperemia are important defense mechanisms in the gastric mucosa. In the rat stomach, we tested the hypotheses that an ulcer-promoting dose of intravenous nicotine 1) reduces ex vivo prostaglandin generation and 2) aggravates mucosal lesions by impairing injury-induced hyperemia. Anesthetized rats were given intravenous control or 4 or 40 micrograms.kg-1.min-1 nicotine infusion. In study 1, ex vivo generation of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (stable metabolite of prostacyclin) was determined by vortexing the mucosal tissue, followed by radioimmunoassay. No significant difference in prostaglandin generation was found between the control and experimental groups. In study 2, intravenous nicotine (40 micrograms.kg-1.min-1) produced a significant rise (19 +/- 3%) in mean blood pressure and completely abolished the gastric hyperemia produced by intragastric saline (2 M). The extent of the associated gastric mucosal injury was significantly increased (from 5.3 +/- 0.8 to 17.4 +/- 5.2% of the corpus mucosa), while the maximum depth of the largest lesions was not affected by intravenous nicotine. The data confirm that the gastric hyperemia associated with gastric mucosal exposure to hypertonic saline plays an important role in limiting the extent of gastric mucosal damage. We conclude that in the rat stomach 1) an ulcer-promoting dose of intravenous nicotine does not significantly inhibit cyclooxygenase activity, and 2) the same does of intravenous nicotine exacerbates hypertonic saline-induced gastric mucosal injury by a mechanism that involves inhibition of injury-induced hyperemia.
Contribution of the large hepatic veins to postsinusoidal vascular resistance
Authors: Maass-Moreno R. , Rothe C. F.
Published: December 2017

We tested the hypothesis that the larger (greater than 2 mm ID) hepatic veins are the primary site of the portal-to-caval venous pressure gradient in the dog. Double-lumen catheters were inserted through the caval wall into hepatic veins of pentobarbital sodium-anesthetized dogs. One lumen opened at the end, and the other to the side. Each catheter was advanced until stopped and then it was withdrawn. The pressure at either port dropped from 87 +/- 31 to 13 +/- 11% of the portal-to-caval pressure difference as each moved past a transition point (TP). The location of the TP depended on the catheter diameter. Intraportal histamine or norepinephrine, 4 and 2.6 micrograms.min-1.kg body wt-1 respectively, augmented only the pressure measured upstream to the TP. A mathematical model of flow through a vessel with a catheter inside predicted a marked increase in resistance when the ratio of catheter OD to vessel ID exceeded approximately 0.6. Autopsy revealed ratios greater than 0.6 upstream to the TP. A hydraulic model confirmed that this effect caused the appearance of the TP. Given the depth (11.7 cm) at which near caval pressures could be found, even during histamine administration, we conclude that the major pressure gradients in the canine liver must lie upstream to the large hepatic veins.