bluuebunny/crossref_metadata_2025 huggingface dataset:
Ability of prostaglandin to reduce ethanol injury to dispersed chief cells from guinea pig stomach
Authors: Cherner J. A. , Naik L. , Tarnawski A. , Brzozowski T. , Stachura J. , Singh G.
Published: December 2017

To determine whether prostaglandin exerts a direct action on individual gastric epithelial cells that protects them from ethanol-induced injury, dispersed chief cells from guinea pig stomach were pretreated with 16,16-dimethyl-prostaglandin E2 (dmPGE2) or placebo before incubation with ethanol or control. Cell injury was assessed in terms of exclusion of Fast Green dye, release of lactate dehydrogenase, alterations of ultrastructure, and pepsinogen secretion stimulated by a variety of secretagogues. Of chief cells 60 +/- 2% were stained by Fast Green if incubated with 10% ethanol for 1 h after pretreatment with placebo, whereas only 38 +/- 1% of cells showed Fast Green staining when pretreated with 2.6 microM dmPGE2 before ethanol exposure. Similarly, 63 +/- 2% of cellular lactate dehydrogenase was released from chief cells pretreated with placebo compared with 36 +/- 4% of lactate dehydrogenase released from cells pretreated with 2.6 microM dmPGE2 (P less than 0.01). The prostaglandin's protective effect persisted throughout a 6-h incubation with ethanol. Scanning and transmission electron micrographs demonstrated disintegration of chief cells pretreated with placebo before ethanol exposure, whereas ultrastructural architecture was relatively preserved among chief cells pretreated with dmPGE2. Preincubation with 8 or 10% ethanol inhibited the subsequent stimulation of pepsinogen secretion caused by carbachol, cholecystokinin, A23187, 12-O-tetradecanoylphorbol 13-acetate, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with dmPGE2 did not reduce the ethanol-induced inhibition of secretion stimulated by any of these secretagogues. These data indicate that dmPGE2 significantly reduces ethanol-induced damage to dispersed chief cells in terms of alterations of membrane permeability and ultrastructure but does not prevent the ethanol-induced impairment of pepsinogen secretion. These findings provide evidence that dmPGE2 exerts a direct but limited protective action on the gastric chief cell, independent of vascular, paracrine, or neural actions.
Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors
Authors: Von Schrenck T. , Heinz-Erian P. , Moran T. , Mantey S. A. , Gardner J. D. , Jensen R. T.
Published: December 2017

To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas. Esophagus bound both tracers, whereas pancreas bound only 125I-[Tyr4]bombesin. In each tissue binding was saturable, dependent on pH, on time, and on temperature, reversible, and specific. Autoradiography demonstrated binding of both tracers only to the muscularis mucosae of the esophagus and binding of 125I-[Tyr4]bombesin diffusely over pancreatic acini. In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae. In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B. Similar relative potencies were found for stimulation of enzyme secretion from dispersed pancreatic acini. Computer analysis in both tissues demonstrated only a single binding site. The present study demonstrates that rat esophagus muscle possesses specific receptors for bombesin-related peptides. Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin. In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
Fate of milk calcium in the gastrointestinal tract of suckling rats
Authors: Simmons M. A. , Henning S. J.
Published: December 2017

In the rat, as in many other mammals, the majority of milk Ca is associated with casein micelles. Because luminal proteolysis is immature in the suckling rat, we investigated the hypothesis that milk Ca remains in the macromolecular form as it traverses the stomach and upper small intestine. When intestinal contents of rat pups were examined 1 h after gavage with 45Ca-milk, 98% of the 45Ca was found to be in a soluble form. Surprisingly, chromatography on Sephadex G-10 showed it to have a molecular weight in the range of that of Ca2+. Analysis of gastric contents showed the stomach to be the initial site of release of Ca from the casein micelles. Although only 45% of the 45Ca was in a soluble form in stomach contents, 100% of this soluble 45Ca behaved as Ca2+. Comparison with the fate of 32P from milk confirmed the suggestion that most of the Ca is released as Ca2+. In vitro studies suggested that this release is the result of simple dilution or the combined action of intrinsic milk enzymes and dilution. Because milk Ca appears to enter the small intestine as Ca2+, we presume its mechanism of absorption in suckling animals is the same as that already established using simple salts of Ca. Nevertheless, the slow release from the bound form may be important in establishing the physiological pattern of Ca absorption in the infant. Implications of this for the supplementation of milks for low-birth-weight human infants is discussed.
Quasielastic light scattering evidence for vesicular secretion of biliary lipids
Authors: Cohen D. E. , Angelico M. , Carey M. C.
Published: December 2017

We employed quasielastic light scattering, negative-stain, and freeze-fracture electron microscopy to study the time-dependent physicochemical behavior of biliary lipids in fresh rat bile. Three to five minutes after bile collection, the earliest light scattering measurements and electron microscopy revealed unilamellar vesicles (mean hydrodynamic radius, Rh = 430-740 A) coexisting with mixed micelles (Rh = 20-120 A) in all biles. Both percent biliary vesicles (1 to greater than 70%) and micellar sizes varied inversely with bile salt concentration (range 1.6-72 mM) both during endogenous pool drainage and sodium taurocholate infusion. With bile salt concentrations in the vicinity of or below the estimated critical micellar concentration, biliary vesicle concentrations remained constant or increased slightly with passage of time. However, with micellar bile salt concentrations, complete conversion of vesicles to micelles occurred at rates that were directly proportional to bile salt concentration. Back-extrapolation of weighted Rh averages of micelles plus vesicles as functions of time gave sizes of approximately 470 A at 1 min, suggesting the predominance of homogeneously sized unilamellar vesicles at the earliest stages of bile formation. After micellization of lipids, mixed protein aggregates of vesicle size were demonstrated in all biles. These experiments elucidate the dynamic coexistence of lipid vesicles and mixed micelles in cholesterol unsaturated biles and demonstrate that vesicle-to-micelle interconversions of biliary lipid aggregates are normal physiological phenomena within the biliary tree.(ABSTRACT TRUNCATED AT 250 WORDS)
Ontogeny of basolateral membrane lipid composition and fluidity in small intestine
Authors: Schwarz S. M. , Bostwick H. E. , Danziger M. D. , Newman L. J. , Medow M. S.
Published: December 2017

To evaluate physicochemical properties of the small intestinal basolateral cell surface during postnatal development, membranes were isolated from suckling (14-17 days) and weanling-mature (35-49 days) rabbit jejunal and ileal enterocytes at 30- to 40-fold purification (based on Na+-K+-ATPase specific activity) and with limited contamination from coisolated cellular elements. Membrane lipid analysis demonstrated age-dependent reductions and proximal to distal increases in total lipid (per milligram protein). Postnatal increases in membrane total cholesterol of jejunum (suckling vs. mature, 0.18 vs. 0.26 mumol/mg protein; P less than 0.01) and ileum (0.18 vs. 0.31 mumol/mg protein; P less than 0.01) resulted in markedly higher cholesterol-to-phospholipid molar ratios (jejunum, 0.43 vs. 0.73; ileum, 0.43 vs. 0.72 mumol/mg protein; P less than 0.01). Membranes from mature animals had higher relative sphingomeylin and phosphatidylcholine content and, in both age groups, fatty acyl saturation was increased in ileum compared with jejunum. By utilization of the fluorophores 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, the fluidity of basolateral membranes and liposomes prepared from extracted membrane lipid decreased markedly in mature rabbits. Arrhenius plots demonstrated higher apparent thermotropic transition temperatures of mature membrane lipid. These data therefore demonstrate significant changes in small intestinal basolateral membrane lipid composition and fluidity that occur during the weaning period. Possible relationships to ontogenesis of membrane protein function are discussed.
A model study of the regulation of gastric acid secretion
Authors: Van Duijn B. , Ypey D. L. , de Goede J. , Verveen A. A. , Hekkens W.
Published: December 2017

A computer simulation model is presented of the gastric phase regulation of gastric acid secretion in humans. The model is based on experimental data from the literature and includes terms representing gastric pH and gastric volume-dependent gastrin secretion, gastrin-dependent acid secretion, food storage in the stomach, and gastric emptying. We have explored the predictive value of the model in assessing the relative importance of gastric pH-dependent and gastric volume-dependent acid secretion mechanisms under various conditions. Similarly we have studied the role of gastric acid deregulation in achlorhydria, the Zollinger-Ellison syndrome, and duodenal ulcer, and the influence of the antacid drugs cimetidine and ranitidine under duodenal ulcer conditions. Model analysis of normal gastric acid regulation suggests that gastric volume-controlled acid secretion is of major importance during eating and predicts that pH-dependent gastrin secretion is of major importance in preventing excessively low pH levels between meals and during the night.
Brain stem responses to electrical stimulation of ventral vagal gastric fibers
Authors: Barber W. D. , Yuan C. S.
Published: December 2017

The brain stem neuronal responses to electrical stimulation of gastric branches of the ventral vagal trunk serving the proximal stomach were localized and evaluated in anesthetized cats. The responses were equally distributed bilaterally in the region of nucleus solitarius in the caudal brain stem. The mean latency of the response was 289 +/- 46 (SD) ms, which translated into a conduction velocity of less than 1 m/s based on the distance between the stimulating and recording electrodes. The responses consisted of single and multiple spikes that showed slight variability in the latency, indicating orthodromic activation via a synapse in approximately 98% of the responses recorded. Forty two percent of the units tested showed evidence of convergence of input from vagal afferent fibers in different branches of the ventral vagal trunk that served the proximal stomach. The resultant activity pattern of the unitary response appeared to be the product of 1) the gastric sensory input or modality conveyed by the afferent source and 2) the time of arrival and diversity of modalities served by other gastric afferents impinging on the unit. This provides a mechanism capable of responding on the basis of specific sensory modalities that dynamically reflect ongoing events monitored and conveyed by other gastric afferents in the region.
Hypoxic liver cell death: critical Po2 and dependence of viability on glycolysis
Authors: Anundi I. , de Groot H.
Published: December 2017

Viability of isolated hepatocytes was not significantly dependent on oxygen at oxygen partial pressures (Po2) from 70 to 0.3 mmHg. The critical Po2 for induction of hypoxic cell death was close to 0.1 mmHg and was distinct from the value at which mitochondrial function becomes impaired (2-5 mmHg). Hypoxic damage in hepatocytes from fasted rats occurred within 1 h but was delayed by the addition of fructose, which increased rates of lactate formation from about 1 to 12 nmol.10(6) cells-1.min-1. Hepatocytes from fed rats maintained viability for almost 180 min of anaerobic incubation and then rapidly became damaged. Addition of fructose prevented hypoxic cell damage also in these hepatocytes. Rates of lactate formation were 11-15 nmol.10(6) cells-1.min-1 and were increased two- to threefold by fructose. The rapid initial degradation of glycogen and the release of glucose were delayed with fructose, which also could have contributed to sustained glycolytic rates. Further, under conditions in which lactate production was high, e.g., in the fed state, there was also a significantly better preservation of cellular ATP levels.
Release of VIP and substance P from isolated perfused canine ileum
Authors: Manaka H. , Manaka Y. , Kostolanska F. , Fox J. E. , Daniel E. E.
Published: December 2017

Basal release of vasoactive intestinal polypeptide (VIP) was 100-fold higher than substance P (SP) release from the vascularly perfused, neurally isolated canine small intestine. High-frequency field stimulation increased SP release but decreased VIP release. VIP release was markedly reduced by tetrodotoxin, perfusion with Ca-free medium, or by hexamethonium but not by atropine. Acetylcholine increased VIP output by an atropine-sensitive mechanism. Methionine-enkephalin or dynorphin (at 10-fold higher concentrations) markedly reduced VIP output; the actions of both these were abolished by naloxone. BHT-920, an alpha 2-adrenoceptor agonist, reduced VIP output markedly by a rauwolscine-sensitive mechanism. Isoproterenol and phenylephrine were without effect. Motilin produced persistent inhibition of VIP output. Thus VIP neurons of isolated canine small intestine were continuously active, driven by intrinsic cholinergic nerves, and subject to presynaptic inhibition by opioid agonists, alpha 2-adrenoceptor agonists, and motilin. This intrinsic neural system may provide tonic inhibitory control to the small intestinal circular muscle and provide a mechanism by which agents may modulate intestinal motor function.
Viability of the vascularly perfused, recirculating rat intestine and intestine-liver preparations
Authors: Hirayama H. , Xu X. , Pang K. S.
Published: December 2017

Function and stability of vascularly perfused, recirculating in situ rat intestine (I) and intestine-liver (IL) preparations were evaluated in fasted and nonfasted rats because these techniques may be readily applied in drug metabolism studies. The rat intestine was perfused with blood medium (7.5 ml/min) via the superior mesenteric artery, with the venous outflow draining into the portal vein, which, together with hepatic arterial flow (2.5 ml/min), constituted the total blood flow (10 ml/min) to the liver. Maintenance of intestinal membrane integrity was observed. Rapid [14C]glucose absorption against a concentration gradient and a lack of [3H]-polyethylene glycol 4000 (PEG 4000, less than 4%) and Evans blue absorption by the recirculating I and IL preparations resulted after bolus injections of these markers into the pyloric end of the duodenum. Other indexes that revealed stable intestinal and liver functions were the following: preservation of reservoir perfusate volume, constancy in perfusion pressure, bile flow, and hemoglobin concentrations, evidence of intestinal glucose utilization and liver glucose production, and a lack of significant leakage of serum glutamic oxalic transaminase. The intestine and liver consumed oxygen at relatively constant rates, but the consumption rates for the fasted tissues (I or L) were significantly higher than those for nonfasted tissues. These results indicate that the vascularly perfused I and IL preparations were maintained in a viable and stable state for a 2-h perfusion period.
Somatostatin release from isolated ganglia of the myenteric plexus
Authors: Grider J. R.
Published: December 2017

Somatostatin neurons of the myenteric plexus project caudad exclusively within the plexus synapsing with neurons in the same or other ganglia. Isolated ganglia offer a unique opportunity to examine peptide transmitter release from these interneurons. Ganglia were isolated from the myenteric plexus by sequential enzymatic digestion, centrifugation, and filtration. Single ganglia were harvested by suction and dispersed in polyacrylamide gel. The ganglia were placed in chambers (200 ganglia/chamber) and perfused with Krebs medium at the rate of 1 ml/min. Addition of the nicotinic agonist, dimethylphenylpiperazinium (DMPP), caused a concomitant increase in somatostatin (152%; P less than 0.001) and vasoactive intestinal peptide (VIP) (79%; P less than 0.05) release above basal level that was abolished by hexamethonium. Addition of the VIP antagonist, VIP-(10-28), (5 microM), to the perfusate augmented significantly DMPP-induced somatostatin release (440%; P less than 0.05), implying that the concomitant release of VIP attenuates somatostatin release. Addition of VIP (1 microM) to the perfusate abolished somatostatin release, confirming the ability of VIP to inhibit somatostatin release. The study shows that VIP interneurons exert a regulatory feedback control over somatostatin interneurons in the myenteric plexus.
VIP and acetylcholine: neurotransmitters in esophageal circular smooth muscle
Authors: Behar J. , Guenard V. , Walsh J. H. , Biancani P.
Published: December 2017

Vasoactive intestinal polypeptide (VIP) and acetylcholine were evaluated as possible inhibitory and excitatory neurotransmitters in the cat esophageal circular smooth muscle. Circular muscle strips 2 mm in thickness were obtained from 1 to 3.4 cm above the lower esophageal sphincter and tested in vitro. Muscle strips contracted with bethanechol (10(-5) M) were relaxed by electrical stimulation (0.5-5 Hz) and by VIP (10(-8)-10(-6) M). Relaxation induced by electrical stimulation was blocked by tetrodotoxin, whereas VIP-induced relaxation was not affected. Highly specific VIP antiserum (5%) antagonized both VIP and electrically induced relaxation, and the antagonism was eliminated when the antiserum was neutralized with VIP (10(-6.5) M). Dopamine (10(-4) M) reduced the relaxation induced both by exogenous VIP and by electrical stimulation but did not affect the relaxation caused by sodium nitroprusside (10(-8)-10(-5) M). In untreated strips, physostigmine (10(-10)-10(-8) M) enhanced the off contraction in response to electrical stimulation, whereas atropine caused a dose-dependent reduction with complete abolition at 10(-4) M. These data suggest that in the esophagus inhibition and excitation are mediated by distinct mechanisms: VIP mediates inhibition and acetylcholine is responsible for the off contraction in response to electrical stimulation.
Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: gastrokinetic effects
Authors: Mawe G. M. , Branchek T. A. , Gershon M. D.
Published: December 2017

Two types of 5-hydroxytryptamine (5-HT) receptor, 5-HT1P and 5-HT3, have been identified physiologically on enteric neurons impaled by intracellular microelectrodes. Activation of 5-HT1P receptors evokes a long-lasting membrane depolarization associated with an increased input resistance, whereas stimulation of 5-HT3 receptors results in a brief depolarization during which the input resistance falls. Slow excitatory postsynaptic potentials (EPSPs) in myenteric type II-hyperpolarizing afterpotential (AH) neurons have been demonstrated to be mediated by 5-HT1P receptors. The current experiments were done to determine whether the substituted benzamide, BRL 24924, is a specific antagonist at 5-HT1P receptors and can be used as a probe to investigate the role played by serotoninergic neurons in the control of gastrointestinal motility. Intracellular microelectrodes were used to analyze the effects of BRL 24924 on guinea pig myenteric neurons. Microejection of BRL 24924 mimicked neither the long-lasting nor the brief response to 5-HT; however, BRL 24924 (0.5-1.0 microM) reversibly antagonized both the long-lasting 5-HT1P receptor-mediated responses of myenteric neurons to 5-HT and 5-HT-mediated slow EPSPs. A greater than 10-fold higher concentration of BRL 24924 was required to reduce the short-lived responses mediated by 5-HT3 receptors. BRL 24924 did not affect the response of myenteric neurons to substance P. These results indicate that BRL 24924 is primarily a 5-HT1P antagonist. Unlike other 5-HT1P agonists or antagonists, BRL 24924 did not block the binding of 5-[3H]HT to 5-HT1P receptors. This observation suggests that specific antagonism of physiological responses to 5-HT by BRL 24924 may be the result of an action on the coupling of the 5-HT1P receptor to its effector mechanism. BRL 24924 (0.5-1 mg/kg) and another 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5 mg/kg), significantly increased the rate of emptying of a 51Cr-labeled liquid meal from the murine stomach. In contrast, the 5-HT3 antagonist, ICS 205-930 (0.1-0.5 mg/kg), did not affect the rate of gastric emptying. These observations are consistent with the hypothesis that intrinsic inhibitory neurons of the murine stomach are activated by serotoninergic axons acting through 5-HT1P receptors. Antagonism of an excitatory drive to neurons in a relaxant pathway may thus explain the gastrokinetic effects of BRL 24924.
Perinatal expression of brush-border hydrolases in rat colon: hormonal and tissue regulations
Authors: Foltzer-Jourdainne C. , Kedinger M. , Raul F.
Published: December 2017

The evolution pattern of brush-border digestive hydrolases and their hormonal regulation were studied in the proximal colon of newborn rats. The potentiality of the colon to express a small intestinal enzymatic pattern was also examined in associations made up of colonic endoderm and small intestinal mesenchyme, developed as either intracelomic grafts in 3-day-old chick embryos or as intrarenal grafts in adult rats. A transient increase of lactase- and aminopeptidase-specific activities occurred in the colon from the 19th day of gestation to 14 days after birth, but sucrase activity could never be detected. Immunocytochemical studies with antibodies specific for rat lactase, aminopeptidase, and sucrase confirmed these results. However, the levels of hydrolase activities were lower in the colon than in the jejunum at the same age. Thyroxine or hydrocortisone treatment during the first 4 days postpartum decreased lactase activity by 70 and 30%, respectively, but did not affect aminopeptidase activity. A slight but significant induction of sucrase activity was obtained with both hormones. In contrast, in the jejunum, only thyroxine decreased lactase activity with a lesser effect (30%), but both hormones increased aminopeptidase activity and induced the marked well-known appearance of sucrase activity. The fetal small intestinal mesenchyme was not able to induce the colonic endoderm to achieve a small intestinal-like differentiation. But the exposure of the developed hybrid intestines to glucocorticoids in organ culture allowed expression of sucrase in one-third of the cases. These results demonstrate the presence of brush-border hydrolases in the proximal colon of newborn rats, normally expressed in the small intestine, but never in the adult colon.(ABSTRACT TRUNCATED AT 250 WORDS)
Phorbol esters induce retrograde myoelectric activity in rabbit ileum in vivo
Authors: Davis R. H. , Mathias J. R.
Published: December 2017

We demonstrated a unique myoelectric response to phorbol esters and a diacylglycerol, 1-oleoyl-2-acetyl-snglycerol, in rabbit ileal loops. This retrograde activity, the orad migrating complex (OMC), was devoid of slow-wave distortion or alterations in slow-wave frequency. The OMC was not inhibited by the cyclooxygenase inhibitor indomethacin or enhanced by addition of the calcium ionophore A23187. The OMC occurred after 4 beta-phorbol 12-myristate 13-acetate, a phorbol ester known to activate protein kinase C, and after 4 alpha-phorbol 12,13-didecanoate, one that does not. Therefore, these studies provide initial evidence that the myoelectric activity induced by phorbol esters and a diacylglycerol is most likely in addition to the activation of protein kinase C.
Palmitate uptake by cultured hepatocytes: albumin binding and stagnant layer phenomena
Authors: Burczynski F. J. , Cai Z. S. , Moran J. B. , Forker E. L.
Published: December 2017

We compared uptake of palmitate by hepatocyte monolayers with uptake by polyethylene membranes under conditions of identical binding and stirring. Hepatocytes and polyethylene display similar clearances when the fatty acid is free, reflecting partial rate limitation by diffusion across the unstirred water layer. When palmitate is 99.8% bound to albumin, however, hepatocytes clear free fatty acid about seven times faster than does polyethylene. We analyzed the uptake of palmitate by polyethylene at two different pHs to isolate the diffusive resistance of the unstirred layer and to show that codiffusion of bound and free palmitate to the hepatocyte surface accounts for only approximately 20% of the albumin-dependent increment in the clearance of free palmitate. The clearance data are supported by independent measurements of the stagnant layer thickness obtained from indicator dilution data and by an electrochemical method. The findings suggest that hepatocytes facilitate the dissociation of albumin-palmitate complexes. Alternatively, albumin may modulate the uptake capacities of hepatocytes and/or polyethylene.
Effects of various agents on ileal postprandial motor patterns and transit of chyme in dogs
Authors: Siegle M. L. , Ehrlein H. J.
Published: December 2017

Effects of intravenous infusions of somatostatin, methionine-enkephalin, and 5-hydroxytryptophan on canine ileal motor patterns and transit of chyme were investigated postprandially. Motility was recorded by multiple closely spaced extraluminal strain gauges. By a computerized method, the length of contraction spread and other motility parameters were evaluated. Transit rates were measured fluoroscopically. Somatostatin and methionine-enkephalin initiated a mixing activity by reducing the incidence and the length of spread of contraction waves induced by a noncaloric meal. Methionine-enkephalin, but not somatostatin, decreased both the number of contractions per minute and the motility index. 5-Hydroxytryptophan converted the mixing activity induced by a nutrient meal into a propulsive pattern. The incidence and the length of spread of contraction waves as well as the number of contractions per minute, the contraction force, and the motility index were enhanced. Results suggest that somatostatin, methionine-enkephalin, and 5-hydroxytryptophan are effective modulators of ileal propulsive activity. Effects are largely similar to those observed in the proximal jejunum, although the lengths of contraction spread and the transit rates were generally less in the ileum.
Role of cholecystokinin in intestinal phase and meal-induced pancreatic secretion
Authors: Dale W. E. , Turkelson C. M. , Solomon T. E.
Published: December 2017

Amylase secretion and plasma cholecystokinin (CCK) were measured in dogs in the interdigestive state and after exogenous CCK-8 and CCK-39 (12.5 to 400 pmol.kg-1.h-1), intestinal sodium oleate, tryptophan plus phenylalanine, HCl (0.74, 2.2, 6.7, 20 mmol/h), and a meat meal (20 g/kg). Interdigestive plasma CCK did not vary, although amylase output showed periodic 15-fold increases. Plasma CCK increased linearly after doubling doses of CCK-8 and CCK-39; the slope of plasma CCK-39 vs. dose was 2.8 times steeper than that of CCK-8, suggesting a longer circulating half-life. At similar plasma concentrations, CCK-8 and CCK-39 were equipotent for stimulating pancreatic secretion. Sodium oleate and tryptophan plus phenylalanine significantly increased plasma CCK and amylase secretion in a load-dependent pattern and were equipotent for both effects. HCl stimulated bicarbonate secretion but not plasma CCK or amylase secretion. Food significantly increased plasma CCK and amylase secretion. Amylase responses to intestinal stimulants and food were significantly greater than to exogenous CCK at low plasma CCK levels. Maximal amylase responses to intestinal stimulants were similar to that after CCK-39 but occurred at 10-fold lower plasma CCK levels. These results indicate that CCK and other factors interact to regulate pancreatic responses to food and intestinal stimulants in dogs.
Colonic motor response to a meal in dogs
Authors: Sarna S. K. , Lang I. M.
Published: December 2017

We investigated the effects of ingestion of a meal on colonic motor activity in six conscious dogs, each instrumented with seven strain-gauge transducers to record circular muscle contractions. A 1,300-kcal meal was given after a 4-h control recording. The post-prandial period of 8 h was subdivided into an early period lasting 2 h and a late period lasting 6 h. The ingestion of the meal did not disrupt the colonic migrating myoelectric complexes (CMMCs) but prolonged their cycle length in the early postprandial period. The cycle length was not different from the control during the late postprandial period. The mean and total duration of contractile activity per hour increased significantly during the early postprandial period in the distal colon but not in the proximal or the middle colon. During the late postprandial period the mean and total duration of contractile activity per hour increased significantly throughout the colon. Giant migrating contractions occurred rarely during the 8-h postprandial period. We conclude that different parts of the colon respond to the ingestion of a meal in different ways. The response also depends on whether the fresh digesta has reached the colon. The late postprandial response is likely to be due to the entry of fresh digesta into the colon.
Isolation and characterization of a mucosal triacylglycerol pool undergoing hydrolysis
Authors: Tipton A. D. , Frase S. , Mansbach C. M.
Published: December 2017

Absorbed and processed mucosal neutral lipid has been shown to be composed of at least two pools of triacylglycerol. One is likely to subserve chylomicron formation, and the other appears to be transported from the intestine via a nonlymphatic route. In the present study, 50 +/- 5% of the mucosal lipid pellets was centrifuged at 75,000 g.min [low-speed pellet (LSP)]. Discontinuous sucrose density gradient centrifugation of LSP showed that 61 +/- 7% of the lipid banded at the 0.25-0.86 M sucrose interface. Neutral lipid analysis showed that this subfraction was only 58% triacylglycerol, suggesting it was undergoing hydrolysis. Active lipolytic activity in vitro was found on incubation. The lipase had an alkaline pH optimum (pH 8.5) and persisted despite pancreatic ductular diversion. Lipolysis in vivo in a LSP fraction was shown by infusing [14C]glyceryltrioleate for 3.5 h followed by [3H]glyceryltrioleate for 30 min. Discontinuous sucrose density centrifugation of the LSP followed by an analysis of the lipids at the 0.25-0.86 M sucrose interface showed that 14C-neutral lipids were only 70 +/- 6% triacylglycerol, whereas 3H-neutral lipids were 88 +/- 2% triacylglycerol. 3H entered LSP slowly compared with the floating lipid in the same centrifuge tube. These studies suggest both in vivo and in vitro mucosal lipolysis by a specific, alkaline-active lipase. The turnover rate of LSP is likely to be slow by comparison with neutral lipid floating to the top of the centrifuge tube.
Intramural neural control of opossum sphincter of Oddi
Authors: Helm J. F. , Dodds W. J. , Christensen J. , Sarna S. K.
Published: December 2017

We evaluated the intramural neural control of the opossum sphincter of Oddi (SO) in an in vitro preparation. Force transducers were used to record contractions at four sites along the sphincter segment. To stimulate intramural nerves, 10- to 120-s trains of pulses (4-10 V amplitude, 0.5 ms duration, and 5 Hz frequency) were delivered to one of three electrode pairs implanted along the SO. Electrical stimulation in the proximal, mid, or distal SO elicited phasic contractions that invariably originated in the proximal SO and propagated antegrade along the entire length of the sphincter segment. Stimulus-evoked contractions resembled spontaneous antegrade peristaltic contractions, but occurred at a higher rate (12-20/min). Atropine completely blocked this excitatory response to nerve stimulation. After atropine, nerve stimulation in the proximal, mid, or distal SO abolished spontaneous contractions at and distal to the site of stimulation for the duration of the stimulus. The inhibitory response to nerve stimulation was completely blocked by tetrodotoxin but was unaffected by phenoxybenzamine, tolazoline, or propranolol. We conclude that 1) the opossum SO is innervated by intramural cholinergic excitatory nerves and nonadrenergic noncholinergic inhibitory nerves; 2) cholinergic excitatory nerves are organized in ascending neural pathways, whereas nonadrenergic noncholinergic inhibitory nerves descend along the length of the SO; and 3) these neural pathways may modulate SO peristalsis in vivo and participate in ascending excitatory and descending inhibitory reflexes.
Ca2+ requirement for metabolic effects of secretagogues in the amphibian gastric mucosa
Authors: Subero O. , Lobo P. , Chacin J.
Published: December 2017

The role of extracellular Ca2+ in metabolic effects induced by theophylline and histamine was investigated in the isolated toad gastric mucosa. Primary and secondary effects on metabolism were differentiated by using K(+)-free solutions, which blocked the secretory responses but not the metabolic ones. The stimulation of respiration induced by theophylline and histamine was dose dependent and was significantly decreased by Ca2(+)-free solutions. In the presence of 1.8 mM Ca2+, the rate of glycogen breakdown was increased by theophylline in a dose-dependent manner and the dose-response curve was somewhat similar to that obtained with oxygen uptake. This effect was inhibited by incubation in Ca2(+)-free solutions. Ca2+ stimulated the rate of glycogen utilization in a concentration-dependent manner. The rates of oxidation of exogenous glucose and pyruvate were significantly inhibited by Ca2(+)-free solutions in theophylline- and histamine-stimulated mucosa, whereas the rates of oxidation of butyrate and acetate were not significantly affected. The Ca2+ ionophore A23187 significantly stimulated the rate of oxygen uptake and this response was not blocked by omeprazole and Sch 28080, two specific inhibitors of gastric H(+)-K(+)-ATPase. The results indicate that Ca2+ is required for optimal stimulation of carbohydrate catabolism in the toad gastric mucosa.
Lipid mediators of inflammation in gastric ulcer
Authors: Wallace J. L.
Published: December 2017

The interest in lipid mediators of inflammation as potential contributors to the pathogenesis of gastric ulcer has increased markedly over the past 20 yr. Although a great deal is known about the actions of mediators such as leukotrienes, thromboxane, and platelet-activating factor in experimental models of ulceration, evidence supporting a role for these mediators in human gastric ulcer is sorely lacking. This review attempts to answer a number of questions regarding the contribution of these mediators to the pathogenesis of gastric ulceration and the possible use of specific inhibitors, antagonists, and dietary manipulation in the treatment of gastric ulcer. Potential directions for future research in this field are suggested as are some of the pitfalls to be avoided in such studies.
Intrahypothalamic corticotropin-releasing factor elevates gastric bicarbonate and inhibits stress ulcers in rats
Authors: Gunion M. W. , Kauffman G. L. , Tache Y.
Published: December 2017

The effects of intrahyopthalamic microinfusions of corticotropin-releasing factor (CRF) on gastric bicarbonate, acid, and pepsin content and on cold restraint-induced gastric lesion formation were tested in three experiments. Bilateral microinfusions of CRF into the hypothalamic ventromedial nucleus (0.86 nmol/rat) significantly increased both gastric bicarbonate concentration and total bicarbonate output. These effects were observed irrespective of whether rats were pretreated with the acid antisecretory drug omeprazole. In nonomeprazole-pretreated rats, CRF microinfusions also significantly reduced acid secretion and raised pH. The increase in bicarbonate content accounted for half of the observed decrease in acid output, suggesting that CRF microinfusions activated separable bicarbonate-stimulating and acid-inhibiting hypothalamic systems. In non-omeprazole-pretreated rats, CRF microinfusions significantly increased serum gastrin, whereas pepsin output was unchanged. Gastric mucosal damage produced by 4 h of cold restraint was significantly diminished by CRF microinfusion into the ventromedial hypothalamus. These data demonstrate that ventromedial hypothalamic microinfusions of CRF increase bicarbonate content, decrease gastric acid content, and confer protection against cold restraint-induced gastric mucosal damage. Hypothalamic CRF neuronal terminals and receptors may be involved in the central regulation of gastric bicarbonate secretion as well as acid secretion.
Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration
Authors: Zimmerman B. J. , Grisham M. B. , Granger D. N.
Published: December 2017

The objective of this study was to determine whether hydrogen peroxide, iron, and/or hydroxyl radicals play a role in ischemia/reperfusion (I/R)-induced granulocyte infiltration in the feline small intestine and whether a chemoattractant is formed when superoxide or hydrogen peroxide reacts with feline extracellular fluid. In vivo determinations of granulocyte infiltration consisted of measurements of tissue myeloperoxidase activity in either the intestinal mucosa (I/R studies) or dermis (chemotaxis studies), whereas in vitro measurements of granulocyte migration were obtained using a Boyden chamber. Treatment with either catalase or the iron chelator deferoxamine significantly attenuated granulocyte infiltration into the mucosa induced by reperfusion of the ischemic intestine. Two hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU), were also evaluated for their ability to modulate I/R-induced granulocyte infiltration. DMTU significantly attenuated the I/R-induced granulocyte accumulation, whereas DMSO had no effect. In other experiments, we were unable to stimulate granulocyte migration with feline plasma exposed to superoxide-generating systems using both in vitro and in vivo models of leukocyte chemotaxis. However, hydrogen peroxide in the presence of either ferrous iron or hemoglobin did significantly increase the chemotactic activity of cat plasma. The results obtained from our studies suggest that either hydrogen peroxide or radical species derived from the interaction of superoxide and hydrogen peroxide with iron elicit I/R-induced granulocyte infiltration in the intestine.
Isobaric intestinal distension in humans: sensorial relay and reflex gastric relaxation
Authors: Azpiroz F. , Malagelada J. R.
Published: December 2017

To determine the relationship between perception of segmental intestinal distension and the reflex gastric tone response, we performed in eight healthy volunteers graded isobaric distensions (2.5 min duration at 10 min intervals) of the duodenum and the jejunum using an electronic barostat. We measured gastric tone as intragastric air volume by a separate barostat and the perception score by a graded questionnaire. At the threshold distending pressure for discomfort in the duodenum (23 +/- 2 mmHg), both perception (5.7 +/- 0.2 score; P less than 0.01) and reflex gastric relaxation (148 +/- 35 ml delta gastric vol; P less than 0.01) were elicited. Lower pressures (12 mmHg below the discomfort threshold) failed to produce perception (0.6 +/- 0.4 score), but significant relaxation was still induced (63 +/- 22 ml delta gastric vol; P less than 0.05). In contrast, no significant gastric relaxation occurred at any pressure level tested in the jejunum (up to 27 +/- 2 mmHg), whereas the perception scores paralleled those produced by duodenal distension. This dissociation between symptoms and visceral reflexes suggests that both responses are independently induced by specific mechanisms.
Intestinal ornithine decarboxylase: half-life and regulation by putrescine
Authors: Iwami K. , Wang J. Y. , Jain R. , McCormack S. , Johnson L. R.
Published: December 2017

Ornithine decarboxylase (ODC) is the primary rate-limiting enzyme for polyamine synthesis. ODC levels are increased in most tissues, including the intestinal mucosa, by growth-promoting agents. This enzyme has a brief half-life of from 5 to 30 min in mammalian tissues and is regulated by its product; putrescine. The current study examines the turnover and regulation of ODC in the mucosa of the small intestine. With the use of scraped intestinal mucosa from cycloeximide-treated rats, the time course of the decline in ODC activity yielded a half-life of approximately 22 min. Labeling enzyme protein with [3H]difluoromethylornithine (DFMO) resulted in a nearly identical estimation of half-life. ODC activity of mucosa from isolated gut segments stimulated by luminal glycine (0.1-0.4 M) was enhanced 60-100% by 10 mM putrescine administered luminally. Putrescine alone had no effect on ODC. In contrast, 10(-7) M putrescine prevented 80% of the ODC activity stimulated by asparagine in IEC-6 cells (a rat intestinal crypt cell line). The half-life of ODC in unstimulated IEC-6 cells was 20 min and increased to 35 min in cells exposed to 10 mM asparagine. These data demonstrate that ODC of nonproliferating villous cells is regulated differently from the identical enzyme in proliferating crypt cells. Therefore, conclusions regarding mucosal growth should not be based totally on ODC activity from whole mucosa, since it is essentially a measure of only the enzyme present in the villous cells.
Effect of histamine and 1,4-methylhistamine on gastric vascular resistance in dogs
Authors: Wood J. G. , Wicina G. M. , Cheung L. Y.
Published: December 2017

The goal of this study was to compare the relative potency of histamine and its metabolite, 1,4-methylhistamine, as vasodilators of the gastric circulation. Changes in vascular resistance were measured during local intra-arterial infusion of graded doses of histamine and 1,4-methylhistamine to an ex vivo segment of dog stomach. Infusate concentrations were adjusted to deliver calculated arterial blood concentrations of 0, 3.7, 11, 33, 100, 300, and 900 ng/ml of each substance to the stomach segment. We found that histamine caused rapid dose-related decreases in gastric vascular resistance of up to -47.6 +/- 1.3% compared with control values. The effects of histamine were reversible when infusions ended. In contrast, there were no statistically significant changes in vascular resistance at any dose of 1,4-methylhistamine. In addition, modifications to previous methods using histamine antagonists resulted in greater attenuation of histamine-induced gastric vasodilation. Our results support a role for locally released histamine, but not for 1,4-methylhistamine, as a mediator of gastric vasodilation.
Ouabain-sensitive K(+)-ATPase in epithelial cells from guinea pig distal colon
Authors: Watanabe T. , Suzuki T. , Suzuki Y.
Published: December 2017

We have previously shown that an ouabain-sensitive H(+)-K+ exchange mechanism may be present in the apical membrane of guinea pig distal colon [Y. Suzuki and K. Kaneko. Am. J. Physiol. 256 (Gastrointest. Liver Physiol. 19): G979-G988, 1989]. The present study is aimed to demonstrate the presence of an ATPase responsible for this exchange. ATPase activity was determined in the crude membrane fraction of the colonic epithelial cell homogenate. ATPase activity under Na(+)-free conditions was increased by the addition of K+, with a half-maximal effect at 55 microM. This increase was completely abolished by 1 mM ouabain, suggesting the presence of an ouabain-sensitive K(+)-ATPase. The ouabain-sensitive K(+)-ATPase activity was inhibited by vanadate (100 microM) and N,N'-dicyclohexylcarbodiimide (100 microM) but was resistant to oligomycin (4.5 micrograms/ml) and NaN3 (1 mM). The ouabain-sensitive K(+)-ATPase activity was observed in the distal but not in the proximal colon, whereas Na(+)-K(+)-ATPase activity was distributed along the entire colon. Omeprazole (40 microM) reduced the colonic K(+)-ATPase activity by 31 +/- 6%, whereas it reduced the gastric K(+)-ATPase activity by 78 +/- 8%. These results suggest that the ouabain-sensitive K(+)-ATPase as demonstrated here is responsible for the colonic H(+)-K+ exchange. This ATPase could be similar to but is not identical with either Na(+)-K(+)-ATPase or gastric H(+)-K(+)-ATPase.
Regulation of cholecystokinin secretion by food, hormones, and neural pathways in the rat
Authors: Lewis L. D. , Williams J. A.
Published: December 2017

Regulation of cholecystokinin (CCK) secretion was studied in conscious unrestrained rats by simultaneous duodenal perfusion with foodstuffs, intravenous infusion of hormones or neural agents, and arterial blood sampling for CCK bioassay. Duodenal infusion of casein resulted in elevation of plasma CCK from fasting level of 0.5 +/- 0.1 to 3.8 +/- 0.4 pM. Casein hydrolysate, calcium, and glucose did not elevate plasma CCK. Infusion of intact fat had a small, but nonsignificant, effect (1.4 +/- 0.4 pM), whereas infusion of oleate increased plasma CCK to 3.7 +/- 0.6 pM. Thus intact protein and fatty acids are the major dietary intestinal stimuli for CCK release in the rat. The CCK response to protein could be inhibited by somatostatin but not by peptide YY (0.2, 2, or 20 micrograms.kg-1.h-1); intravenous infusion of 1 or 10 micrograms.kg-1.h-1 somatostatin decreased casein-stimulated CCK levels to 1.5 +/- 0.2 and 0.9 +/- 0.3 pM, respectively. Stimulation of vagal discharge with 2-deoxy-D-glucose had no effect on basal or protein-stimulated plasma CCK levels; thus CCK release in the rat does not appear to be modulated by central vagal pathways. Gastrin-releasing peptide increased fasting plasma CCK levels to 1.6 +/- 0.1 pM. Administration of the cholinergic agonist bethanechol, while having no effect on fasting CCK level, inhibited protein-stimulated plasma CCK from 3.9 +/- 0.6 to 1.3 +/- 0.3 pM. Cholinergic blockade with atropine, in contrast, had no effect on basal or protein-stimulated plasma CCK. Thus CCK release is stimulated by dietary protein or fatty acid and by gastrin-releasing peptide and inhibited by somatostatin and bethanechol.