bluuebunny/crossref_metadata_2025 huggingface dataset:
Is intestinal transport of sugars and amino acids subject to critical-period programming?
Authors: Karasov W. H. , Solberg D. H. , Chang S. D. , Hughes M. , Stein E. D. , Diamond J. M.
Published: December 2017

Physiological responses include three sorts: reversible within an individual's lifetime, fixed irreversibly at some critical period in life, and genetic. Examples of the first and third but not the second sort have been demonstrated for intestinal nutrient transport. Hence, we searched for critical-period programming of sugar and amino acid transport by mouse small intestine. Mice were maintained on either of two rations from gestation through birth, lactation, and weaning until adulthood: a high-carbohydrate, maintenance-protein ration and a carbohydrate-free, high-protein ration. The two groups of mice were then compared in adulthood while both groups were on the former or the latter ration. Early diet has irreversible effects on gut and body size; because of higher growth rates until weaning mice receiving high-carbohydrate diets achieved and maintained higher weights, longer guts, and heavier proximal guts than the mice receiving carbohydrate free diets. This difference increased with litter size and may have arisen from limitations on nursing mothers' ability to convert dietary protein into milk carbohydrate or fat. Early diet appears to exert some general effects on adult intestinal transport as a result of these differences in body and gut size but does not appear to exert specific irreversible effects on transport of D-glucose, L-proline, L-leucine, L-lysine, or L-aspartate or on passive glucose permeability. Active and passive glucose transport increases reversibly on a high-carbohydrate diet, whereas amino acid transport increases reversibly on a high-protein diet.
Pancreaticobiliary factors in the modulation of small intestinal enterokinase in the rat
Authors: Newman B. M. , Lee P. C. , Tajiri H. , Cooney D. R. , Lebenthal E.
Published: December 2017

Chronic pancreaticobiliary diversion was employed to study the modulation of enterokinase in the small intestine of adult rats. Diversion resulted in apparent trophic changes of the proximal bypassed portion of the intestinal mucosa. An almost complete loss of mucosal enterokinase activity in the proximal duodenum but no increase of enterokinase in the segments distal to reentry of the common duct was found in the pancreaticobiliary-diverted rats. The effect on the enterokinase activity in the proximal segment was specific in that no other brush-border enzymes measured in that segment were decreased. The decrease in enterokinase was partially prevented by dietary supplementation with pancreatic trypsinogen and completely avoided with the addition of a combination of bile acids and trypsinogen. Supplementation with bile acid alone did not preserve the enterokinase levels in the bypassed rats. The results suggested that trypsinogen is the primary factor responsible for modulating enterokinase levels in the proximal small intestine, with bile acids acting as a modifier.
Na-H exchange in rat liver basolateral but not canalicular plasma membrane vesicles
Authors: Moseley R. H. , Meier P. J. , Aronson P. S. , Boyer J. L.
Published: December 2017

Na+-stimulated H+ movement and H+-stimulated Na+ uptake were studied in basolateral (blLPM) and canalicular (cLPM) rat liver membrane vesicles. H+ movement was monitored with the fluorescent amine acridine orange; 22Na uptake was assayed by a rapid Millipore filtration technique. In blLPM, inwardly directed Na+ gradients stimulated H+ efflux and outwardly directed Na+ gradients stimulated proton influx. Outwardly directed proton gradients (pH in 5.9/pH out 7.9) stimulated initial 22Na uptake rates 5- to 10-fold over pH-equilibrated conditions (pH in 7.9/pH out 7.9). Conversely, inwardly directed proton gradients (pH in 7.9/pH out 5.9) inhibited 22Na uptake. pH-dependent 22Na uptake was inhibited by amiloride and harmaline but not by other transport inhibitors, bumetanide, furosemide, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and acetazolamide. Lithium also inhibited H+-stimulated 22Na uptake. Although a component of pH-stimulated 22Na uptake appeared to be dependent on membrane potential, this electrogenic component was amiloride insensitive. Proton gradient-stimulated 22Na uptake in blLPM was saturable, with a Km of 5.4 mM and a Vmax of 14 nmol . min-1 . mg prot-1. In contrast, in cLPM, no Na+ gradient-stimulated proton movement and no pH-dependent Na+ uptake occurred. These findings establish an electroneutral Na-H antiport in blLPM but not cLPM in rat liver. The polarity of this exchanger supports a model of bile formation that is dependent, in part, on canalicular HCO-3 and/or OH- excretion.
Effect of selective muscarinic antagonists on peristaltic contractions in opossum smooth muscle
Authors: Gilbert R. J. , Dodds W. J.
Published: December 2017

In this study we examined the role of M1- and M2-muscarinic receptors in the mediation of circular smooth muscle esophageal contractions elicited by pharmacological cholinergic stimulation and during peristalsis in anesthetized opossums. Esophageal-body contractions were induced by bethanechol administration, whereas peristalsis was elicited by pharyngeal stroking or cervical vagal stimulation. Contractions were measured by a low-compliance manometric recording system. The incidence and amplitude of bethanechol-induced contractions were antagonized by 4-diphenylacetoxy-n-methylpiperidine (4-DAMP) and atropine but not pirenzepine. 4-DAMP and atropine caused an increased velocity, decreased amplitude, and preferential reduction of the incidence of primary peristaltic contractions in the proximal smooth muscle esophagus. During long-train vagal stimulation, intra-stimulus A-waves had a velocity similar to primary peristalsis, whereas poststimulus B-waves showed a velocity considerably faster than primary peristalsis. Short-train vagal stimulation produced a contraction sequence, termed an "S-wave," that had a velocity similar to that of the A-wave. At low doses 4-DAMP increased the velocity and decreased the amplitude of A-wave and S-wave contractions, and at high doses 4-DAMP abolished both the A-wave and S-wave contractions. B-wave contractions were minimally affected by 4-DAMP. Pirenzepine had no effect on contractions induced by swallows or vagal stimulation. We conclude that M2-muscarinic receptors mediate esophageal contractions in the circular smooth muscle during primary peristalsis and during A-waves and S-waves induced by vagal stimulation, and M1-receptors do not have any important role in the excitatory neural pathway to the esophagus.(ABSTRACT TRUNCATED AT 250 WORDS)
Actomyosin, collagen, and cell hypertrophy in intestinal muscle after jejunoileal bypass
Authors: Bowers R. L. , Eeckhout C. , Weisbrodt N. W.
Published: December 2017

Previous observations indicate that bypass of 70% of the small bowel of rats induces increases in the seromuscular mass of both the in-continuity and the bypassed segment. The purpose of this study was to quantify the amount of actomyosin and collagen in the muscle layer and to determine the number of cells per cross-sectional area of the circular muscle layer at various locations of the small intestine after jejunoileal bypass. The amount of actomyosin relative to total tissue protein remained the same in the hypertrophied tissues compared with controls, and the actin-to-myosin ratios were similar. The collagen content per wet weight of the tissue from the sham- and bypass-operated animals tended to be less than in tissue from unoperated controls and was significantly less at the distal in-continuity location. The number of cells per cross-sectional area was decreased in tissues from all locations of the bypassed animals. These findings support the hypothesis that the increase in seromuscular mass after intestinal bypass is due to an increase in functioning smooth muscle tissue and that at least part of the increase is due to cell hypertrophy.
Mechanism of inhibition of gastric acid secretion by SCN-: interrelation of SCN- flux and inhibition
Authors: Reenstra W. W. , Forte J. G.
Published: December 2017

Effects of thiocyanate (SCN-) and imidazole on acid secretion and Cl- flux across the isolated bullfrog gastric mucosa have been examined. For open-circuited mucosae, with Cl- Ringer on the nutrient side and 110 mM Na isethionate on the secretory side, the addition of 15 mM SCN- to either the secretory or nutrient side gave equivalent reductions in acid secretion (JH) and nutrient-to-secretory Cl- flux (JnsCl) . JnsSCN, the nutrient-to-secretory flux of SCN- (0.2 mu eq . cm-2 . h-1), was much less than the decrease in JH (1.88 mu eq . cm-2 . h-1). Addition of imidazole, phosphate, or histidine to the secretory side reversed SCN- inhibition of JnsCl. Addition of imidazole to the nutrient side gave equivalent restorations of JnsCl and JH. The increase in JnsSCN, 0.07 mu eq . cm-2 . h-1, was much less than the increase in either JH, 0.77, or JnsCl, 0.86 mu eq . cm-2 . h-1. Similar results were obtained for mucosae bathed with NaCl on the secretory side. With 15 mM SCN- on both sides, the flux ratio for Cl- was significantly larger (1.0) than the flux ratio for SCN- (0.47). The addition of nutrient imidazole increased the flux ratios for Cl- and SCN- to 1.29 and 1.16, respectively. Both SCN- and Cl- showed exchange diffusion. Inhibition of acid secretion with nutrient SCN- at short circuit also inhibited JnsCl but did not alter the partial conductance of Cl-.(ABSTRACT TRUNCATED AT 250 WORDS)
Somatostatin induces ectopic activity fronts via a local intestinal mechanism during fed state or pentagastrin
Authors: Schippers E. , Janssens J. , Vantrappen G. , Vandeweerd M. , Peeters T. L.
Published: December 2017

The effect of local intra-arterial infusions of somatostatin on small bowel motility in the postprandial period and during an intravenous pentagastrin infusion was studied in five dogs. A Silastic catheter was implanted in a small branch of the superior mesenteric artery perfusing a 5-to 10-cm jejunal segment located 30-40 cm distally to Treitz. Small bowel myoelectric activity was recorded by means of a series of bipolar electrodes implanted subserosally along the small intestine. Experiments were started 2 wk after surgery and were performed in conscious animals. Intra-arterial infusion of somatostatin induced activity fronts in the fed state and during intravenous pentagastrin infusion in a dose-dependent manner. These activity fronts always started at or just below the perfused segment, migrated distally over the remaining small bowel, and were superimposed on the fed pattern. We conclude that local administration of somatostatin is able to initiate normally migrating ectopic activity fronts, despite the presence of neural and hormonal factors that control the fed state. Local release of somatostatin might be involved in the initiation of spontaneously occurring activity fronts.
Effects of taurodeoxycholate on in vivo water and solute transport in rat jejunum in absence and presence of calcium
Authors: Ammon H. V. , Cho D. S. , Loeffler R. L. , Reetz K. L.
Published: December 2017

Bile acids and fatty acids enhance the permeability of brush-border membrane vesicles for calcium. It has been postulated that increased influx of calcium into the enterocyte might be responsible for the fluid secretion induced by dihydroxy bile acids and fatty acids. During in vivo perfusion studies of the rat jejunum, 15 mM taurodeoxycholate induced secretion of electrolytes and water (P less than 0.001), reduced glucose absorption (P less than 0.001), and enhanced the absorption of mannitol (P less than 0.0125) and calcium (P less than 0.001). Calcium absorption continued to be enhanced during perfusion of a CaCl2-containing solution following the perfusion with taurodeoxycholate (P less than 0.05). In view of the previously demonstrated enhanced permeability of the apical brush-border membrane in the presence of bile acids, it is very likely that some calcium enters the enterocyte along the steep concentration gradient in the presence of taurodeoxycholate. In spite of enhanced calcium absorption, 15 mM CaCl2 had no effect on control absorption rates or on fluid secretion induced by taurodeoxycholate. The data indicate that the effects of bile acids on intestinal transport are not mediated by an influx of calcium into the enterocyte.
Quantification of axial forces in rectum-anal canal of the cat
Authors: Krier J. , Adams T.
Published: December 2017

A newly developed probe was used to measure in vivo axial forces in the rectum-anal canal of the anesthetized cat. Spontaneous contractions of the smooth muscle of the internal anal sphincter were recorded, as were neurally evoked contractions of striated muscle of the external anal sphincter. Bilateral electrical stimulation (1-10 V, 1-5 Hz, 0.05 ms duration) of motor axons in pudendal nerves elicited two responses. One was synchronous phasic contractions of skeletal muscle fibers of the external anal sphincter that were not abolished by atropine but were by gallamine trithiodide. They occurred at short latencies (1-2 ms) and were mediated through low-threshold (1-3 V, 0.05 ms duration) efferent axons in the pudendal nerves. Contraction times ranged from 45 to 60 ms, and contraction duration ranged from 100 to 160 ms. The second response was a progressive elevation in tone of the anal canal due to contractions either of the smooth muscle of the rectum and/or that of the internal anal sphincter. The elevation in smooth muscle tone concomitant with pudendal nerve stimulation may be due to reflex activation of cholinergic neural pathways, since the response was abolished by atropine.
Boundary cells between longitudinal and circular layers: essential for electrical slow waves in cat intestine
Authors: Suzuki N. , Prosser C. L. , Dahms V.
Published: December 2017

Electrical slow waves were recorded by intracellular electrodes and by quasi-intracellular pressure and suction electrodes from muscle fibers at different levels in edgewise preparations of cat jejunum. Simultaneous recordings from longitudinal and circular muscle layers showed similar resting potentials from either muscle layer near the boundary zone, and lower resting potentials in cells of circular muscle near the submucosa. Slow waves were maximal in amplitude at the boundary between the two layers and spread electrotonically away from the boundary in both layers. Bipolar recordings were of opposite polarity on the two sides of the boundary. Amplitudes of slow waves from inner circular fibers were significantly lower than from outer circular fibers. Small strips of each muscle layer were prepared with or without the attached interstitial cells of Cajal plexus as identified by methylene blue staining. Either muscle layer showed slow waves from regions where interstitial cells of Cajal (ICC) were observed after the recording. No slow waves were recorded from either layer from regions where ICC were not observed. Strips containing ICC but not strips lacking ICC could be driven electrically. Since blocking of neurons does not abolish slow waves and since regions of muscle lacking ICC do not have slow waves, it is concluded that the interstitial cells (ICC-I) are most likely the boundary elements essential for slow waves in either layer of intestinal muscle.
Effects of tachykinins on gastric acid and pepsin secretion and on gastric outflow in the Atlantic cod, Gadus morhua
Authors: Holstein B. , Cederberg C.
Published: December 2017

Gastric acid and pepsin responses to substance P, physalaemin, eledoisin, and an eledoisin-related peptide, [Lys6]eledoisin-(6-11), were measured in gastrically and intestinally perfused cods. The intestinal perfusion maintains water balance and inhibits drinking. During basal conditions acid secretion was stimulated (approximately equal to 25%) by low doses (less than 0.13 nmol X kg-1 X h-1) of physalaemin and eledoisin. High doses (greater than 16 nmol X kg-1 X h-1) were inhibitory. Median and very high doses of substance P and eledoisin-related peptide, respectively, tended to stimulate acid secretion. All tachykinins were extremely efficacious pepsigogues. Physalaemin and eledoisin were the most potent (D50 approximately 10(-10) mol X kg-1 X h-1) but produced fading and submaximal responses at high doses. The fading persisted despite endogenous acidification produced by histamine stimulation. Relative to physalaemin, the potencies of substance P and eledoisin-related peptide were 0.04 and 0.001. The results suggest that some tachykinin may be a physiological stimulator of pepsin secretion and that the effect on acid secretion results from activation of both stimulatory and inhibitory pathways. The inhibitory component probably includes a cholinergic link. Gastric volume outflow increased during infusion of physalaemin, eledoisin, and (slightly) substance P. The response, which was not related to acid secretory rate (and conceivably not to volume secretion), suggests that a tachykinin may be involved also in the regulation of drinking.
Inhibition of gastrin release by gastric inhibitory peptide mediated by somatostatin
Authors: Wolfe M. M. , Reel G. M.
Published: December 2017

The present studies were directed to examine the effect of gastric inhibitory peptide (GIP) on gastrin release and to determine the potential role of somatostatin in mediating this effect, utilizing rat antral mucosa in short-term tissue culture. Antral mucosa was incubated at 37 degrees C in Krebs-Henseleit buffer (pH 7.4) continuously gassed with 95% O2-5% CO2. Inclusion of carbachol (2.5 X 10(-6) M) in the culture medium increased media gastrin concentrations from 3.29 +/- 0.76 (SE) (control) to 6.77 +/- 0.76 ng/mg tissue prot (P less than 0.02). Rat antral mucosa was then incubated in the presence of GIP (10(-10) to 10(-7) M) to determine its effect on carbachol-stimulated gastrin release. GIP significantly inhibited carbachol-stimulated gastrin release into the culture media at all concentrations examined. To determine whether inhibition of carbachol-stimulated gastrin release by GIP was mediated by somatostatin, antral mucosa was incubated in the presence of carbachol, GIP (10(-10) to 10(-7) M), and specific antibodies to somatostatin in excess. Inclusion of antibodies to somatostatin in the culture medium abolished the capacity of GIP (10(9) to 10(-7) M) to inhibit carbachol-stimulated gastrin release. Results of these studies indicate 1) that GIP inhibits carbachol-stimulated gastrin release and 2) that, under the conditions of these experiments, GIP inhibition of gastrin release may be mediated locally through release of antral somatostatin.
Measurement of function in isolated single smooth muscle cells
Authors: Bitar K. N. , Makhlouf G. M.
Published: December 2017

Smooth muscle cells, isolated from the stomach of guinea pig, were anchored electrostatically to a poly-L-lysine-treated cover slip that formed the ceiling of a minichamber. The cells could be perfused at high flow rates for long periods without being dislodged. Contractile responses, measured by image-splitting micrometry, were obtained repeatedly and reproducibly at intervals of 5 s-5 min for up to 3 h. Peak response in single cells was attained in 1.5-2 min by comparison with peak response in suspensions of muscle cells (0.5 min). The delay was probably due to unstirred layers covering anchored single cells. Otherwise, the magnitude of response of single cells and their sensitivity to various agonists (C-terminal octapeptide of cholecystokinin, methionine-enkephalin, and acetylcholine), as expressed in the D50 values, were identical to those obtained from measurements on large populations (suspensions) of muscle cells. The identity of dose-response profiles of single cells and suspensions of cells, particularly the wide span of the dose-response curves and the low Hill coefficients (0.30-0.35), implied that receptor heterogeneity was an inherent property of each muscle cell rather than a reflection of differences between muscle cells. This simple, precise, and economical method offers notable advantages in studies of isolated smooth muscle cells.
Cellular messengers of stimulants of pepsinogen secretion from isolated frog esophageal mucosa
Authors: Shirakawa T. , Hirschowitz B. I.
Published: December 2017

The messenger roles of Ca2+ and cyclic nucleotides in the stimulation of pepsinogen secretion by three classes of stimuli [muscarinic (bethanechol), peptidergic (bombesin), and adrenergic (isoproterenol)] were studied in vitro using the peptic gland-bearing esophageal mucosa from the American bullfrog, Rana catesbeiana. Pepsinogen secretion was stimulated in a dose-dependent manner by the calcium ionophore A23187, by dibutyryl cAMP (DBcAMP), and by isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor. Isoproterenol and bethanechol increased the tissue cAMP content in the presence of IBMX. IBMX, which by itself stimulated secretion, was potentiating in combination with bombesin, additive with bethanechol, and less than additive with isoproterenol. Omission of Ca2+ from the bathing medium did not alter basal pepsinogen secretion nor the response to maximally effective doses of isoproterenol but partly inhibited the secretory responses to bethanechol and bombesin. Ca2+-free medium with 1 mM EGTA reduced pepsinogen secretion under all basal and stimulated (including A23187- but not DBcAMP-stimulated) conditions, indicating a critical role for Ca2+ in the secretion of pepsinogen secretion. A23187 by itself produced only an initial (15-20 min) release of pepsinogen, whereas IBMX and DBcAMP produced a delayed sustained secretion. The combination of A23187 with either IBMX or DBcAMP mimicked the responses to bethanechol or bombesin. These results indicate that both calcium and cAMP may be obligatory and interacting intermediates in the full stimulation of pepsinogen secretion by frog esophageal peptic glands with at least cholinergic and peptidergic stimuli.
Intestinal interaction of bile acids, phospholipids, dietary fibers, and cholestyramine
Authors: Gallaher D. , Schneeman B. O.
Published: December 2017

Binding of bile acids and phospholipids to a number of dietary fibers and cholestyramine (CH) within the small intestine was determined. The fibers used were cellulose, wheat bran, oat bran, guar gum (GG), and lignin (LG). GG, LG, and CH bound significant quantities of bile acids. However, only the CH reduced the bile acid concentration within the aqueous phase of the intestinal contents. Significant phospholipid binding was found only with CH. None of the test substances significantly reduced the quantity of solubilized lipid. Multiple regression analysis indicated that the total quantity of bile acids and phospholipids in the aqueous phase of the intestinal contents was a significant predictor of the quantity of lipid solubilized within the contents (r2 = 0.67). The failure of GG and LG to significantly decrease the amount of solubilized lipid suggests that the hypocholesterolemic effect of these fibers is due more to their bile acid binding capacity than to an effect on lipid solubilization.
Electrolyte permeabilities of pancreatic zymogen granules: implications for pancreatic secretion
Authors: De Lisle R. C. , Hopfer U.
Published: December 2017

Zymogen granules from rat pancreas were prepared on a 40% Percoll gradient at free calcium levels less than 0.2 microM. We have previously shown [Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9)] that zymogen granules prepared by this method are stable in vitro for more than 1 h in "physiological buffers." The electrolyte permeabilities of the zymogen granule membrane were investigated to determine the basis for this stability. Ionic permeabilities were estimated from rates of osmotic lysis and measured as decrease in optical density (OD) of granule suspensions. OD correlated linearly with lysis, as indicated by release of amylase, except for the highest and lowest 10% of the OD of intact granules. Lysis of freshly isolated granules was slow in Na+ or K+ salt solutions (e.g., t1/2 approximately 3 h for Cl-) but was accelerated 5- to 50-fold when cation ionophores were present simultaneously. This behavior indicates that zymogen granules have low endogenous permeabilities to the cations Na+ and K+, but are highly permeable to a variety of anions. Both anion conductance and anion-exchange pathways were found. The relative selectivity of the anion conductance pathway was SCN- greater than Br- approximately NO-3 greater than SO2-(4) greater than acetate- approximately Cl- greater than isethionate-. The relative selectivity sequence for anion/-OH- exchange was acetate- greater than SCN- greater than Br- approximately NO-3 approximately Cl- much greater than isethionate- greater than SO2-(4). The anion transport blocker DIDS blocked the electrogenic pathway with a half-maximal effectiveness at approximately 2 microM. DIDS had little effect on the anion-exchange pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Gamma radiation affects active electrolyte transport by rabbit ileum: basal Na and Cl transport
Authors: Gunter-Smith P. J.
Published: December 2017

The effect of whole-body gamma radiation (5-12 Gy) on electrolyte transport by rabbit ileum in vitro was assessed for 1-96 h postirradiation using the short-circuit technique and radioisotopic fluxes. Although there was no effect of radiation on short-circuit current (Isc), transepithelial potential, or resistance 1 h after exposure, by 24 h the basal parameters of ileal segments isolated from irradiated animals were significantly greater than those of sham-irradiated controls. The Isc increased in a dose-dependent fashion and was greatest 24 h postexposure. Isotope flux experiments revealed that the increased Isc following irradiation resulted in part from a stimulation of active serosal-to-mucosal net Cl flux. There was no observable change in net Na transport. The results demonstrate that radiation exposure alters cellular transport processes, which may contribute to the fluid and electrolyte imbalance observed following radiation exposure.
Ontogeny of gastric mucosal permeability responses to luminal H+ and bile salt in the rat
Authors: Tepperman B. L. , Barr D. B. , Palmer M. C.
Published: December 2017

Gastric mucosal responses to intraluminal instillation of acid (10, 50, and 150 mM HCl) and acidified solutions of sodium taurocholate (10 mM) were measured in rats between 5 and 60 days after birth. Net loss of H+ and gain of Na+, K+, and protein into the gastric lumen remained low and stable up to 25 days after birth. After that there were dose-dependent increases in H+ loss and Na+ and K+ appearance in the gastric lumen. Luminal protein appearance did not change with any concentration of acid tested in any of the ages examined. Gastric instillation of sodium taurocholate resulted in an increase in the rate of H+ loss as well as Na+ and K+ appearance in neonatal rats after 12-14 days. Protein appeared in the recovered gastric instillate and increased in parallel with Na+ and K+. In response to bile salt treatment, ulcers were only evident after 35 days of age. Injection of 8-day-old rats with corticosterone acetate (250 mg/kg) did not affect the ionic fluxes or protein output in response to acid alone or acidified bile salt solutions. These studies indicate that intragastric acid loads did not increase the ionic permeability of the gastric mucosa until 25 days after birth. The permeability changes occur earlier (day 12-14) if sodium taurocholate is added to the acid instillate. Prior to that time the mucosal permeability characteristics of the neonatal rat stomach are not altered by instillation of either acid loads alone or bile salt solutions.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurements of intracellular pH in Necturus antral mucosa by microelectrode technique
Authors: Ashley S. W. , Soybel D. I. , Cheung L. Y.
Published: December 2017

Intracellular pH (pHi) was measured in the surface epithelial cells of Necturus antrum using pH-sensitive intracellular microelectrodes. Electrodes were prepared by filling 10- to 20-M omega resistance glass microelectrodes with a H+ ion-selective exchange resin and calibrated before use in solutions of known pH 4.0-8.0. The electrode response (n = 15) was linear (r = 0.93; P less than 0.001) with a slope of 52.1 +/- 2.3 mV/pH unit. Antral mucosa was mounted in a modified Ussing chamber and pHi was determined from the difference between the potentials recorded by intracellular H+-selective and conventional microelectrodes. These measurements of pHi were validated by examining the response of the intracellular microelectrodes to 1) depolarization of the cell membrane produced by K+ substitution for Na+, and 2) alkalinization and acidification of pHi produced by NH+4 substitution for Na+ in the bathing solutions. In tissues bathed with HCO-3-Ringer solution (pH 7.0), the mean pHi was 7.34 +/- 0.02 with a range from 7.24 to 7.43. In N-2-hydroxymethylpiperazine-N' -ethanesulfonic acid (HEPES)-Ringer solution (pH 7.0), pHi was reduced to 7.02 +/- 0.05 (P less than 0.01). Acidification of the luminal solution to pH 6.8 with CO2 produced a 0.22 +/- 0.04-pH unit fall in pHi (P less than 0.001). In contrast, acidification to pH 4.0 with HCl had no significant effects on pHi. These findings indicate that HCO-3 may play an important role in pHi regulation in this tissue. In addition, they suggest that, in contrast to CO2, the surface epithelial cells of Necturus antrum are relatively resistant to acidification by luminal HCl.
Does corticosterone affect gastric mucosal cell growth during development?
Authors: Tseng C. C. , Johnson L. R.
Published: December 2017

The effect of corticosterone on the growth of the gastric mucosa was investigated during development. The weight of the mucosa and DNA, RNA, and protein content were used as parameters of growth. The pepsinogen content of the oxyntic gland was examined as an indicator of the biological action of corticosterone on development. Corticosterone-treated animals had lower body weights than control animals on days 10-20. This difference was not seen on day 25. Corticosterone administration during the first and second postnatal weeks induced the precocious appearance of pepsinogen in the oxyntic gland mucosa and increased basal acid output. These effects disappeared by day 25. The weight of the mucosa and DNA, RNA, and protein content of the oxyntic gland and antrum increased with age, but corticosterone had no effect on any of these parameters. We conclude that the induction of precocious development of the gastric mucosa by corticosterone is not due to the stimulation of growth.
Sites of resistance changes with inhibition of acid secretion in frog stomach
Authors: Rehm W. S. , Carrasquer G. , Schwartz M.
Published: December 2017

The primary purpose of this study was to determine the sites of resistance changes from thiocyanate inhibition of secretion to better evaluate models of the gastric proton pump. The potential difference, resistance, and H+ secretory rate were measured with various tonicities of the secretory fluid. Thiocyanate (SCN) inhibition generally produces a resistance increase, but with nutrient Ba, the resistance is high and SCN decreases it. The latter effect is also seen with cimetidine. In the secreting fundus a hypotonic secretory solution has a small effect on resistance, but in the inhibited fundus the effect is huge, due to increase of resistance of the lumen-tubular cell pathway. With a hypotonic secretory solution, for inhibited fundus (cimetidine or omeprazole) and antrum, SCN does not decrease the resistance of the surface cells and/or the transintercellular pathways with or without Ba. The SCN resistance decrease with Ba is via the tubular cell pathway. With Ba the resistance of the nutrient membrane of the tubular cells decreases after SCN or cimetidine inhibition. The findings further support the concept that under standard conditions the resistance via the lumina and tubular cells is low and that via the surface cells and transintercellular pathways is high.
Microsphere method in measurement of blood flow to wall layers of small intestine
Authors: Dregelid E. , Haukaas S. , Amundsen S. , Eide G. E. , Soreide O. , Lekven J. , Svanes K.
Published: December 2017

Microspheres of 10.90 +/- 0.65 micron (SD) were injected in the superior mesenteric artery of cats and their intramural distribution and diameter in the small intestine were studied microscopically under basal conditions and after vasodilation by isoproterenol. Approximately 2% of the spheres were shunted through the small intestinal vasculature and could be recovered in the liver. Analysis of the tissue distribution suggested that all spheres arrested in villi represented villous blood flow, spheres arrested in the crypt layer represented flow to the crypts, and the majority of microspheres trapped in the submucosa also represented crypt flow. Nutritive blood flow to the submucosa constituted only 1.5% of total intestinal flow. Log-linear analyses identified factors responsible for sphere distribution, including effects of sphere size, isoproterenol treatment, and local blood flow or vascular resistance. Spheres with diameters greater than 11.08 micron had 1.35 times larger odds than smaller spheres to embolize in the muscularis rather than in the mucosa, but no consistent difference between diameter profiles in the crypts and villi was found. With this reservation, 11-micron spheres seem to be appropriate for measuring blood flow to the muscle, crypt, and villous layers of the small intestine.
Phorbol esters stimulate somatostatin release from cultured cells
Authors: Sugano K. , Park J. , Soll A. , Yamada T.
Published: December 2017

Recent studies suggest that 12-O-tetradecanoylphorbol 13-acetate (TPA), one of a family of phorbol esters that are known tumor promoters, can activate intracellular Ca2+, phospholipid-dependent protein kinase (protein kinase C) directly. To examine the possible involvement of protein kinase C-mediated mechanisms in regulating gastric somatostatin release, we studied the effects of TPA on isolated enriched canine gastric somatostatin cells in short-term culture. TPA markedly stimulated somatostatin release such that nearly 10% of total cellular content of somatostatin was released into media within 2 h of incubation. Among the phorbol compounds tested, TPA was the most potent, with half-maximum effective dose (ED50) obtained at a dose of 5 X 10(-9) M. Phorbol 12,13-dibutyrate (PDBu) also stimulated somatostatin release but with only 5% of the potency of TPA, whereas phorbol compounds with no biological activity in other systems failed to stimulate somatostatin release. In the absence of extracellular Ca2+, the effects of TPA were significantly attenuated. In contrast, stimulation of somatostatin release by forskolin (10(-4) M) was not affected by Ca2+ deprivation but was potentiated by TPA. No such potentiation was observed when TPA was combined with the Ca2+ ionophore A23187. Carbamylcholine (10(-5) M), which inhibits the stimulatory actions of beta-adrenergic agonists or dibutyryl cyclic adenosine monophosphate on somatostatin cells, also inhibited TPA-induced somatostatin release. These data suggest the presence of dual stimulatory mechanisms for gut somatostatin release, both of which are susceptible to inhibition by muscarinic agonists.
Measurement of resistance of barriers to solute transport in vivo in rat jejunum
Authors: Westergaard H. , Holtermuller K. H. , Dietschy J. M.
Published: December 2017

Assessment of intestinal absorptive function requires techniques for correcting transport constants for diffusion barrier resistance. These studies were done to develop such techniques for use in vivo. In one method the functional thickness of the unstirred water layer (d) in rat jejunum was quantitated electrically, and its minimal surface area (Sw) was measured directly. From these values the diffusion barrier resistance (d/Sw) decreased from 0.041 to 0.022 as the perfusion rate of the intestine was increased from 1.5 to 15 ml/min. In the second method apparent passive permeability coefficients (*P) were measured for a series of saturated fatty acids, and these increased with chain length. However, at the longest chain lengths tested, *P became proportional to their free diffusion coefficients, indicating that uptake was limited by the rate of diffusion up to the microvillus surface. From the rates of uptake of such diffusion-limited probes, the diffusion barrier resistance was again calculated and found to decrease from 0.041 to 0.022 as the rate of perfusion was increased from 1.5 to 15 ml/min. Over this same range of perfusion rates, the apparent Michaelis constant (*Km) for D-glucose transport decreased from 18.2 to 10.0 mM. Using either set of resistance terms and these apparent Km values, the true Km value for glucose transport in vivo was found to equal 0.8 mM when the barrier resistance was extrapolated to zero. Thus these data indicate that diffusion-limited probes can be utilized to measure unstirred layer resistance in the intestine of a live animal so that absolute transport parameters can be determined in vivo in experimental animals and, presumably, in humans.
Ion transport by neonatal rabbit distal colon
Authors: Potter G. D. , Burlingame S. M.
Published: December 2017

The neonatal small intestine is characterized by electrical conductance and permeability to ions higher than in the corresponding adult intestine. To investigate whether this property of the neonate is limited to the small intestine, or extends to the colon, a modified Ussing chamber for determination of transmucosal potential difference (PD), short-circuit current (Isc), transepithelial conductance (Gt), and ion fluxes in the neonatal rabbit distal colon was constructed. After care to reduce edge damage, Gt for the neonatal colon was found to be 8.4 +/- 0.3 mS . cm2 and for adult colon in the same chamber, 7.4 +/- 0.5 (P greater than 0.05). Net Na and Cl fluxes under short-circuit conditions were similar to those obtained in adult colon. Unidirectional ion fluxes were also similar to those of the adult. Net Na flux (JNanet) was incompletely inhibited by 10(-4) M of amiloride. Response to replacement of Na, Cl, and HCO3-, respectively, in the bathing solutions was not different from that expected in adult rabbit colon. Thus differences between adult and neonatal rabbit colon were small, and the increased conductance and unidirectional ion fluxes characteristic of the neonatal small intestine were not evident in the neonatal rabbit distal colon.
Intestinal mucosa in diabetes: synthesis of total proteins and sucrase-isomaltase
Authors: Olsen W. A. , Perchellet E. , Malinowski R. L.
Published: December 2017

The effects of insulin deficiency on nitrogen metabolism in muscle and liver have been extensively studied with recent in vivo demonstration of impaired protein synthesis in rats with streptozotocin-induced diabetes. Despite the significant contribution of small intestinal mucosa to overall protein metabolism, the effects of insulin deficiency on intestinal protein synthesis have not been completely defined. We studied the effects of streptozotocin-induced diabetes on total protein synthesis by small intestinal mucosa and on synthesis of a single enzyme protein of the enterocyte brush-border membrane sucrase-isomaltase. We used the flooding-dose technique of McNurlan, Tomkins, and Garlick (Biochem. J. 178: 373–379, 1979) to minimize the difficulties of measuring specific radioactivity of precursor phenylalanine and determined incorporation into mucosal proteins and sucrase-isomaltase 20 min after injection of the labeled amino acid. Diabetes did not alter mucosal mass as determined by weight and content of protein and DNA during the 5 days after injection of streptozotocin. Increased rates of sucrase-isomaltase synthesis developed beginning on day 3, and those of total protein developed on day 5. Thus intestinal mucosal protein synthesis is not an insulin-sensitive process.
Inhibition of ATP levels by quinidine in a human colonic epithelial cell line
Authors: Dharmsathaphorn K. , Huott P. , Cartwright C. A. , McRoberts J. A. , Mandel K. G. , Beuerlein G.
Published: December 2017

The influence of quinidine, a putative K+ channel blocker, on Cl- secretion induced by vasoactive intestinal polypeptide (VIP) was investigated. Quinidine inhibited Cl- secretion induced by VIP in T84 cell monolayers. A similar inhibitory effect of quinidine on Cl- secretion was observed in an isolated human colon. However, in the isolated human colon, which absorbs Na+ avidly, inhibition of Na+ absorption predominated. In the T84 cell, the half-maximal inhibition by quinidine occurred at 60 microM, while 300 microM almost completely inhibited the VIP-induced Cl— secretion. Mucosal addition of quinidine was at least equally effective compared with serosal addition, suggesting that quinidine acts on the apical membrane or intracellularly. Quinidine had little or no effect on VIP-stimulated Cl- efflux in the first 15 min after its addition, suggesting that blockage of the Cl- exit pathway on the apical membrane is an unlikely mechanism. Similarly, quinidine did not inhibit the K+-recycling mechanism on the basolateral membrane in the first 15 min after its addition. The initial inhibitory action of quinidine corresponded better with its ability to decrease cellular ATP levels. Our study suggests that the depletion of cellular ATP levels may explain the initial inhibitory action of quinidine on electrolyte transport in the intestine, while the late effect is multifactorial.
Development of arginine-synthesizing enzymes in mouse intestine
Authors: Hurwitz R. , Kretchmer N.
Published: December 2017

The urea biosynthetic pathway functions in mammalian liver to convert excess ammonia to urea and to maintain the concentration of ammonia in blood at nontoxic levels. This action is accomplished by enzymatic adaptation to quantitative changes in dietary protein. The first two enzymes of the pathway are found in the intestine of the adult mouse, but they do not adapt to dietary change. The enzymes in the intestine produce citrulline, which is carried by the bloodstream to the kidney, where it is converted by the next two enzymes of the pathway to arginine. This mechanism serves as the major source of circulating arginine. We have demonstrated that, at birth, the arginine-synthesizing enzymes in the kidney of the C57Bl/6 mouse are minimally developed, whereas in the intestine activity of carbamoyl-phosphate synthase is elevated and argininosuccinate synthase and lyase, usually present only in trace quantities in the adult intestine, are markedly increased in the newborn. The arginine formed cannot be converted to urea, since arginase does not appear in intestinal cells of the mouse until the age of 15 days. Except for liver, intestine has the most rapid protein turnover of any normal tissue. Our study indicates that, at a time when no other endogenous source of arginine for protein synthesis is available, the intestine of the newborn C57Bl mouse is capable of synthesizing arginine from either citrulline or NH3 and CO2.
Ileal hyperplastic response to starvation in the rat
Authors: Holt P. R. , Wu S. , Yeh K. Y.
Published: December 2017

The ability to respond to changes in the external and internal environments is a fundamental characteristic of intestinal structure and function. We compared the responses of the rat proximal and distal small intestine to the stresses of fasting and refeeding in the rat. In the duodenum, 3 days of starvation caused villus and crypt hypoplasia, reduced incorporation of [3H]thymidine into crypt cells, decreased cell migration rate on the villus, and lowered specific and total activities of several cellular enzymes. These changes were reversed by 1 day of refeeding. In contrast, mucosal hypoplasia did not occur in the ileum during fasting, and the specific activities of the disaccharidases were increased after 3 days of starvation. However, ileal [3H]thymidine incorporation, thymidine kinase activity, and ornithine decarboxylase activity decreased during starvation. These effects were also reversed by refeeding. The results of these studies illustrate differing responses for the proximal and distal small intestine and suggest the presence of distinctly differing mechanisms for the control of their mucosal mass and enzyme activities.
Transcellular sodium transport and intracellular sodium activities in rabbit gallbladder
Authors: Moran W. M. , Hudson R. L. , Schultz S. G.
Published: December 2017

This study was designed to explore the relation between the rate of transcellular active Na+ transport by rabbit gallbladder epithelium, JNa, and the intracellular Na+ activity, (Na)c; the latter was determined by use of highly selective Na+ microelectrodes. The underlying strategy was based on the well-established observation that JNa is stimulated by the presence of bicarbonate in the bathing solutions. Our results confirm previous observations that the addition of bicarbonate to the bathing solutions results in a twofold increase in JNa. In the absence of bicarbonate, (Na)c averaged 16 mM. Within 2–4 min after the addition of bicarbonate to both bathing solutions, (Na)c increased to an average value of 22 mM and then gradually declined and by 15 min did not differ significantly from the value observed in the absence of bicarbonate. Thus, a twofold increase in JNa is not associated with an increase in (Na)c. These results are in accord with earlier observations on Necturus urinary bladder and small intestine and contradict the notion that an increase in the rate of active Na+ extrusion from the cell across the basolateral membrane in response to an increase in the rate of Na+ entry across the apical membrane is necessarily the result of a sustained increase in (Na)c.
Relations among canine intestinal motility, blood flow, and oxygenation
Authors: Kvietys P. R. , Barrowman J. A. , Harper S. L. , Granger D. N.
Published: December 2017

Blood flow, arteriovenous O2 difference, and lumen pressure were measured in isolated loops of canine ileum. Ileal pressure was increased by an intra-arterial infusion of either Met-enkephalin or acetylcholine. Pressures were quantitated using a motility index (MI = mean of the pressure peaks divided by number of contractions per minute). Both Met-enkephalin and acetylcholine increased MI in a dose-dependent fashion. The highest MI achieved with acetylcholine was 37.9 mmHg, while Met-enkephalin produced a maximal MI of 8.1 mmHg. Ileal oxygen uptake increased when MI reached values greater than 6. There was a direct linear relationship between oxygen uptake and MI. Distension of the lumen in the absence of motility resulted in a decrease in oxygen uptake when lumen pressure reached 15–20 mmHg. The results of these studies indicate that contractions of intestinal smooth muscle can increase intestinal oxygen uptake and may contribute to the overall oxygen demands of the gut under conditions of fasting and feeding. Furthermore, large (greater than 20 mmHg) increments in lumen pressure during enhanced motility may compromise intestinal oxygenation.