bluuebunny/crossref_metadata_2025 huggingface dataset:
GRP-producing nerves control antral somatostatin and gastrin secretion in pigs
Authors: Holst J. J. , Knuhtsen S. , Orskov C. , Skak-Nielsen T. , Poulsen S. S. , Nielsen O. V.
Published: December 2017

By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.
Hormonal regulation of adaptive intestinal growth in artificially reared rat pups
Authors: Yeh K. Y. , Yeh M. , Holt P. R.
Published: December 2017

Adaptive growth and precocious expression of sucrase activity occur in the small intestine of artificially reared (AR) rat pups fed a hormone-free diet. The physiological mechanisms underlying adaptive intestinal growth were studied. Day 12 rat pups that received jejunal isografts subcutaneously on day 0 were subjected to artificial feeding and were killed on day 16. Crypt cellularity and DNA labeling index in isografts from AR, but not from mother-fed, rats increased significantly to levels found in in situ host jejunum of AR rats, indicating that humoral regulatory mechanisms are responsible for intestinal cell proliferation in AR pups. Radioimmunoassays of serum corticosterone, thyroxine, insulin, and gastrin and of gastric gastrin contents revealed that only serum corticosterone concentrations were significantly elevated, suggesting that corticosterone plays a critical role for intestinal growth. To examine this possibility directly, day 12 rats were adrenalectomized (ADX) and AR by continuous infusion of diets containing 0, 10, or 50 micrograms/ml corticosterone. Serum corticosterone concentrations paralleled the infused doses of corticosterone. Jejunal DNA labeling index increased in all ADX AR rats at day 13 in a dose-dependent manner. Increased jejunal DNA labeling index was maintained on day 14 in intact AR rats and ADX AR rats fed 10 micrograms/ml corticosterone but not in ADX AR rats receiving 0 or 50 micrograms/ml. We conclude that endogenous corticosterone is one of the systemic factors responsible for the adaptive increase in intestinal growth of AR rats.
Identification of a single sinusoidal bile salt uptake system in skate liver
Authors: Fricker G. , Hugentobler G. , Meier P. J. , Kurz G. , Boyer J. L.
Published: December 2017

To identify the sinusoidal bile acid uptake system(s) of skate liver, photoaffinity labeling and kinetic transport studies were performed in isolated plasma membranes as well as intact hepatocytes. In both preparations photoaffinity labeling with the photolabile bile salt derivative (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-[3 beta-3H]cholan-24-oyl)-2-aminoethanesulfonate revealed the presence of a predominant bile salt binding polypeptide with an apparent molecular weight of 54,000. The labeling of this polypeptide was inhibited by taurocholate and cholate in a concentration-dependent manner and was virtually abolished by 1 mM of the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Kinetic studies of hepatic uptake with taurocholate, cholate, and the photoreactive bile salt derivative indicated the involvement of a single transport system, and all three substrates mutually competed with the uptake of each other. Finally, irreversible inhibition of the bile salt uptake system by photoaffinity labeling of hepatocytes with high concentrations (250 microM) of photolabile derivative reduced the Vmax but not the Km of taurocholate uptake. These findings strongly indicate that a single polypeptide with an apparent molecular weight of 54,000 is involved in sinusoidal bile salt uptake into skate hepatocytes. These findings contrast with similar studies in rat liver that implicate both a 54,000- and 48,000-K polypeptide in bile salt uptake and are consistent with a single Na+-independent transport mechanism for hepatic bile salt uptake in this primitive vertebrate.
Effects of rectal distension on the sphincter ani externus and levator ani muscles in cats
Authors: Dubrovsky B.
Published: December 2017

The response characteristics of levator ani (LA) muscles to rectal distension and its rectified and integrated EMG activity was recorded and compared with the responses of the sphincter ani externus (SAE) to the same stimuli. Experiments were performed in 42 cats anesthetized with chloralose (70 mg/kg) dissolved in a 25% urethan-saline solution. Fast (about 1-2 s) rectal distension (10-40 ml of air were injected into a rubber balloon in the rectum, reaching pressures of up to 80 mmHg) produced a reflex contraction of both LA and SAE muscles. Sustained distension elicited a sustained discharge from the LA muscles that endured for the duration of the distension, up to 2-3 min. These changes were observed in 75% of 210 trials. EMG activity increased from 30 to over 600% of base-line levels, with the majority, 65% of trials, showing greater than 100% increase. In contrast to these excitatory responses of the LA muscles, SAE responded to sustained rectal inflation with inhibition of ongoing activity, an inhibition that could reach muscular silence. Fast intermittent distension, one every 2-3 s, however, produced an increase in the level of activity of the SAE. Analysis of the EMG activity preceding defecation revealed an increase of LA activity 1-2 min before actual expelling. We believe this result to be consistent with the hypothesis that these muscles may contribute to anorectal evacuation. In the anesthetised animal, during the passage of solid material through the anus, the SAE showed increased activity. We believe this to be the result of a local phenomenon, the development of a tonic stretch reflex in the SAE.(ABSTRACT TRUNCATED AT 250 WORDS)
Development of gastrin synthesis and posttranslational processing mechanisms in rats
Authors: Marino L. R. , Sugano K. , Yamada T.
Published: December 2017

To examine the ontogeny of gastrin synthesis and posttranslational processing mechanisms, we utilized region-specific antisera to determine the factors that regulate the contents of gastrin and its precursors in the stomachs of developing rats. Gastrin content increased gradually from birth to a peak at 5 wk of age, after which there was a slight decrease to levels observed in mature animals. Unlike gastrin, glycine-extended precursors of gastrin (G-Gly) increased abruptly in the first day of life but thereafter increased at a steady state. Dexamethasone treatment and early weaning (at 11 days of age) rapidly increased gastrin content, whereas G-Gly content was decreased. On weaning animals to adult rat chow abruptly at an age (18 days) when the corticosteroid surge associated with the weaning process had already occurred, evidence for increases in both gastrin and G-Gly content were observed 7 days later. In contrast, administration of dexamethasone to 18-day-old rats enhanced gastrin content to a greater extent than G-Gly. These results suggest that the natural surge in corticosteroids associated with weaning may enhance gastrin amidation activity, whereas the concomitant dietary changes may exert a stimulatory effect of gastrin synthesis.
Autoregulation in the developing postnatal intestinal circulation
Authors: Nowicki P. T. , Miller C. E.
Published: December 2017

The relationships among perfusion pressure, blood flow, and oxygen uptake were determined in in vitro ileal loops from 3- and 35-day-old swine. Arterial perfusion of the ileal loops was achieved using a reservoir perfusion apparatus that allowed direct manipulation of perfusion pressure. The hematocrit, partial pressure of oxygen, and partial pressure of carbon dioxide of the blood used to perfuse the gut loops were standardized. During steady-state perfusion at an arterial pressure of 100 mmHg and venous pressure of 0 mmHg, ileal loops from 3-day-old swine demonstrated a higher blood flow (55 vs. 27 ml.min-1.100 g-1, 3 vs. 35 day old) and lower arteriovenous oxygen content difference (3.5 vs. 6.6 ml O2/dl). Oxygen uptake was not statistically different between groups (1.99 vs. 1.76 ml O2.min-1.100 g-1). During perfusion pressure reduction from 150 to 25 mmHg (in successive decrements of 25 mmHg), pressure-flow autoregulation was present in ileal loops from 35-day-old swine but not in ileal loops from 3-day-old swine. Similarly, tissue oxygen uptake was more effectively maintained in ileal loops from older swine during perfusion pressure reductions. We speculate that the efficacy of intrinsic regulation of intestinal hemodynamics and oxygenation is dependent, in part, on postnatal age.
Stimulation of rabbit lacrimal gland secretion with biologically active peptides
Authors: Dartt D. A. , Shulman M. , Gray K. L. , Rossi S. R. , Matkin C. , Gilbard J. P.
Published: December 2017

To determine whether biologically active peptides can stimulate lacrimal gland secretion, we measured fluid and protein secretion from the cannulated lacrimal gland excretory duct of anesthetized rabbits after arterial injection of various peptides. Vasoactive intestinal peptide (VIP, 0.003-3 nmol) and porcine histidine isoleucine-containing peptide (PHI, 0.01-3 nmol) stimulated fluid and protein secretion in a dose-dependent manner. Cholecystokinin octapeptide (CCK-8, 0.01-3 nmol) stimulated fluid but not protein secretion. Neither bombesin nor eledoisin in doses as high as 3 nmol stimulated fluid or protein secretion. When combinations of high or low doses of VIP and the cholinergic agonist acetylcholine (ACh) were injected simultaneously, fluid and protein secretion was additive. We concluded that VIP and PHI stimulated secretion of lacrimal gland fluid and protein, CCK-8 stimulated secretion of fluid, and bombesin and eledoisin did not stimulate either fluid or protein secretion. VIP and ACh, both found in lacrimal gland nerve endings, stimulate lacrimal gland fluid and protein secretion by separate pathways.
Effect of bombesin and gastrin-releasing peptide on canine sphincter of Oddi
Authors: Sievert C. E. , Potter T. J. , Levine A. S. , Morley J. E. , Silvis S. E. , Vennes J. A.
Published: December 2017

This study reports the effects of bombesin and gastrin-releasing peptide (GRP) on the canine sphincter of Oddi using a method that allows repeated cannulation of the biliary sphincter in the unanesthetized animal through a Thomas cannula placed opposite the biliary papilla. Immediately after intravenous administration of bombesin or GRP, phasic sphincter contractions disappeared, basal sphincter pressures fell, and common bile duct pressures rose. Because bombesin releases cholecystokinin (CCK) and CCK resulted in a similar pattern to that of bombesin, the bombesin effect on the sphincter of Oddi may have been secondary to CCK's effect on the sphincter. To test if the bombesin effect on the sphincter of Oddi was due to the release of CCK, we blocked CCK release by administration of somatostatin, having first established that somatostatin blocked endogenous CCK release in our animal model by use of an intraduodenal infusion of lipid. Exogenous administration of bombesin failed to alter sphincter of Oddi or common bile duct pressures in dogs treated with somatostatin. Somatostatin did not, however, block CCK's effect on gallbladder contraction, since exogenous administration of CCK after somatostatin injection resulted in the pressure changes in the biliary tree typical of CCK-induced gallbladder contraction. Thus bombesin administration appears to result in sphincter relaxation and gallbladder contraction by the release of endogenous CCK rather than by a direct effect. The increase in common bile duct pressures was due to gallbladder contraction, since this rise in pressure was abolished by cholecystectomy. The peptide effect on sphincter contraction and basal sphincter pressure were unaffected by cholecystectomy.
Effect of prostaglandins on the ontogenic response of rat gastric mucosa to luminal H+
Authors: Thorn C. E. , Soper B. D. , Tepperman B. L.
Published: December 2017

We have characterized the ontogeny of gastric mucosal permeability responses to luminal H+ and investigated the effect of prostaglandins (PGs) on these responses in the neonate. Mucosal responses to instillation of HCl (100-600 mN) were measured in rats between 10 and 60 days after birth. Permeability changes were expressed as H+ loss and Na+, K+, and protein appearance in the luminal instillate. Responses to 100 and 200 mN HCl were low at all ages. Instillation of 300 or 400 mN HCl produced larger transmucosal fluxes of ions and protein in animals older than 20 days of age compared with younger animals. High concentrations of acid (500-600 mN HCl) produced large fluxes of ions and protein at every age examined. The responses in suckling animals were less than those seen in rats 25 days of age or older. In each age group mucosal HCO-3 secretion was inhibited by HCl concentrations greater than 100 mN. In each age group the mucosal response to 350 mN HCl was reduced by either 16,16-dimethyl-PGE2 (2 micrograms/kg ig) or a PGI2 analogue (Iloprost; 100 micrograms/kg ig). The effect of either prostanoid was greater in animals younger than 25 days of age compared with older rats. PGE2 and 6-keto-PGF1 alpha were detected in the gastric mucosa at all ages examined. Suckling animals had higher levels of either prostanoid. PGE2 levels decreased after 30 days, while levels of 6-keto-PGF1 alpha remained constant. These data suggest that 1) the susceptibility of H+-induced alterations in mucosal permeability to ions and protein increases as the animal ages, 2) the gastric mucosa of weanling rats is sensitive to PGs, and 3) PGE2 and 6-keto-PGF1 alpha are present in neonatal rat mucosa.
Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis
Authors: Ulrich-Baker M. G. , Wang P. , Fitzpatrick L. , Johnson L. R.
Published: December 2017

Refeeding fasted rats induces a dramatic trophic response in gastrointestinal mucosa and is associated with elevations in both the rate of DNA synthesis and ornithine decarboxylase (ODC) activity. The signal for these increases is unknown. Amiloride prevents cell alkalinization by blocking Na+-H+ exchange at apical epithelial cell membranes. In study 1, rats were fasted 48 h, treated with amiloride (0.5 to 500 mg/kg), and refed for 4 h. Refeeding increased ODC activities in the jejunal mucosa (X8) and liver (X19) but not in the oxyntic gland mucosa. In the jejunum, but not the liver, the activation of ODC was completely abolished by 100 mg/kg amiloride. In study 2, the rate of DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation 16 h after refeeding. Refeeding resulted in significantly increased rates of DNA synthesis (dpm.microgram DNA-1.30 min-1) over fasted levels, and amiloride at 100 mg/kg significantly reduced the elevations in the jejunum and liver. In conclusion, amiloride inhibits the postprandial increases in jejunal ODC activity and DNA synthesis in the jejunum and liver. The results indicate that 1) the Na+-H+ antiport is essential to the increased ODC activity in the jejunum and the stimulation of DNA synthesis in the jejunum and liver after a meal and 2) increases in DNA synthesis and their suppression by amiloride are not necessarily linked to ODC activity.
Stimulation of taurocholate and glycocholate efflux from the rat hepatocyte by arginine vasopressin
Authors: Kuhn W. F. , Gewirtz D. A.
Published: December 2017

Vasopressin induces alterations in the transmembrane distribution of the bile salts taurocholate and glycocholate but not of cholate, chenodeoxycholate, or chenodeoxycholate derivatives in isolated rat hepatocytes in suspension. Studies were conducted to define the specific transport events modulated by vasopressin. Unidirectional uptake of cholate, taurocholate, and glycocholate, monitored within a 15-s time frame, is not altered by vasopressin. Km values for cholate, taurocholate, and glycocholate influx were found to be 57, 12, and 26 microM, respectively. Vmax values for influx of cholate, taurocholate, and glycocholate were 1.7, 1.8, and 2.4 nmol.mg protein-1.min-1, respectively. At half-maximal effective concentrations, arginine vasopressin increases unidirectional efflux of taurocholate by 34% (EC50 = 1.5 X 10(-9) M) and glycocholate by 17% (EC50 = 5 X 10(-9) M). In the presence of 0.05 microM arginine vasopressin, the apparent Km value for taurocholate efflux decreases from 1.57 mM (control) to 0.94 mM; for glycocholate, the apparent Km decreases from 5.19 mM (control) to 3.22 mM. Vasopressin does not significantly change the Vmax values for taurocholate and glycocholate efflux (0.40 and 1.05 nmol.mg protein-1.min-1, respectively). These studies suggest that modulation of bile salt efflux by vasopressin may be utilized to probe bile salt transport pathways in the rat hepatocyte.
Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney
Authors: McKelvey T. G. , Hollwarth M. E. , Granger D. N. , Engerson T. D. , Landler U. , Jones H. P.
Published: December 2017

Previous studies have proposed and supported a role for the proteolytic, irreversible conversion of xanthine dehydrogenase to xanthine oxidase (XO) in postischemic injury in a wide variety of organs. A second mechanism of conversion, due to sulfhydryl modification and reversible with dithiothreitol (DTT), is potentially important but has not been well investigated. In this study rat liver and kidney were found to produce significant amounts of DTT-reversible XO during normothermic global ischemia. Formation of reversible XO precedes that of irreversible XO by approximately 0.5 h with a strong correlation (r = 0.92) existing between the rate of irreversible XO formation and the concentration of reversible XO. The formation of reversible XO is preceded by a depletion of glutathione with concentrations of glutathione during ischemia correlating (r = 0.85) with the observed concentration of reversible XO. While a large increase in the extent of liver damage occurs concurrently with conversion in an in vivo liver model of liver ischemia, an ischemia-reperfusion regimen (1 h of ischemia plus 0.5 h of reperfusion) that resulted in no conversion caused significant elevations in serum glutamic pyruvic transaminase and serum glutamic-oxaloacetic transaminase. Rats depleted of XO by tungsten dieting release 65% less enzyme after the same insult, suggesting that endogenous XO may also participate in the damage process independent of any conversion.
Small intestine as possible source of increased plasma cGMP after administration of alpha-hANP to dogs
Authors: Ito K. , Yukimura T. , Takenaga T. , Yamamoto K. , Kangawa K. , Matsuo H.
Published: December 2017

A synthetic alpha-human atrial natriuretic peptide (alpha-hANP) was infused into the renal artery of anesthetized dogs, and the urine flow, renal hemodynamics, and plasma guanosine 3',5'-cyclic monophosphate (cGMP) were determined. alpha-hANP led to a natriuresis accompanied by an increase in renal blood flow in the infused kidney but not in the contralateral kidney. The systemic blood pressure remained unchanged. The arterial plasma cGMP significantly increased after alpha-hANP administration. The plasma cGMP in the renal vein was significantly lower than that in the aorta throughout the experiment; therefore the elevated circulating cGMP was probably of extrarenal origin. The plasma cGMP in the right ventricle and femoral vein was also increased to the same extent seen in the aorta. On the other hand, plasma cGMP in the superior mesenteric vein was remarkably increased over that in the aorta. After the administration of alpha-hANP, the increased circulating cGMP seems to be the result of an enhancement of production of this nucleotide from the small intestine or organs drained by the superior mesenteric venous circulation.
Kinetics of binding of cholecystokinin to pancreatic acini
Authors: Wank S. A. , Jensen R. T. , Gardner J. D.
Published: December 2017

In the present study we examined the kinetics of binding of iodinated COOH-terminal octapeptide of cholecystokinin (125I-CCK-8) to its receptors on dispersed acini prepared from guinea pig pancreas. At 37 degrees C, binding of 125I-CCK-8 reached a steady state after 60 min of incubation. Dissociation of bound 125I-CCK-8 was biphasic, indicating that the labeled peptide binds in two distinct states: a rapidly dissociating state and a slowly dissociating state. Binding of 125I-CCK-8 in the rapidly dissociating state was maximal within 3 min of incubation, did not depend on incubation temperature or cellular energy metabolism, could be stripped by 0.5 M potassium thiocyanate, and showed accelerated dissociation with CCK-8 or dibutyrylguanosine 3',5'-cyclic monophosphate (Bt2cGMP). Binding of 125I-CCK-8 in the slowly dissociating state was maximal after 60 min of incubation, was decreased by reducing the incubation temperature or inhibiting cellular energy metabolism, was not stripped by 0.5 M potassium thiocyanate, and did not show accelerated dissociation with CCK-8 or Bt2cGMP. Increasing the concentration of 125I-CCK-8 increased the fraction of radioactivity bound in the rapidly dissociating state. When binding of 125I-CCK-8 reached a steady state, nearly all of the bound radioactivity was in the slowly dissociating state. Computer analysis of the inhibition of 125I-CCK-8 by CCK-8 under experimental conditions where the rapidly dissociating state predominates demonstrated a complete loss of high-affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice
Authors: Fioramonti J. , Fargeas M. J. , Bueno L.
Published: December 2017

The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with 51Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK.
Physiological enteric stimulation elicits cardiovascular reflexes in the rat
Authors: Pittam B. S. , Ewart W. R. , Appia F. , Wingate D. L.
Published: December 2017

By use of anesthetized rats, parameters for the activation of cardiovascular reflexes by stimulation of gastric or hepatic receptors have been established. For reflex activation, the mean minimum intragastric volume was 4 ml, and the mean minimum rate of hepatic portal vein infusion was 0.3 ml/min. Subdiaphragmatic vagotomy affected the response to gastric distension but did not appear to affect the response to hepatic portal vein infusion, indicating that vagal afferents are involved in mediating gastric-cardiovascular but not hepatic-cardiovascular reflexes. Experiments designed to emphasize the vagal component of the response to gastric distension confirmed this finding. Antagonist effects indicated that the tachycardia was mediated by beta-adrenoreceptor stimulation and that the pressor response was mainly mediated by alpha-adrenoreceptors. The data show that stimuli used in experiments to assess central processing of sensory information from the gastrointestinal tract can activate cardiovascular reflexes. Caution in the design of such experiments and in the interpretation of the data generated is indicated.
Analysis of sequential events in intestinal absorption of folylpolyglutamate
Authors: Darcy-Vrillon B. , Selhub J. , Rosenberg I. H.
Published: December 2017

Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of "natural" folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.
Experimental models of gastric ulceration and injury
Authors: Silen W.
Published: December 2017

There are inumerable experimental models of gastric mucosal epithelial injury. Many of these currently in wide use can be regarded as unphysiological and severe, rarely encountered in humans. An analysis of more physiological and simple models indicates that little is known of the events that ultimately cause cellular death, even in simple and easily controllable systems. A review of acceptable measures of gastric mucosal injury is presented. It is suggested that studies of subtle physiological injuries at the cellular level are more likely to yield meaningful insights into the causation of gastric mucosal ulceration.
Inactivation of human lipase by proteases
Authors: Thiruvengadam R. , DiMagno E. P.
Published: December 2017

To determine if human lipase is inactivated by trypsin and chymotrypsin, we intubated 22 human subjects with an oroduodenal tube and stimulated pancreatic secretion with cholecystokinin octapeptide. The duodenal aspirate from each subject was divided into a control and a test sample and incubated in a 37 degrees C water bath for 2 h. An inhibitor of trypsin or chymotrypsin or more of one of these enzymes was added to the test sample. We found that the loss of lipase activity was partly prevented by inhibiting trypsin with aprotinin (910 KU/ml; P = 0.03) and was accelerated by adding bovine trypsin (2.5 mg/ml; P = 0.01). Inhibiting chymotrypsin with turkey egg white (2.5 mg/ml) totally abolished the loss of lipase activity (P = 0.01), and addition of bovine chymotrypsin (5 mg/ml) accelerated the loss of lipase activity more than adding trypsin (P = 0.01). After inhibiting chymotrypsin (to maintain lipase activity), increasing trypsin activity by adding a single or repeated doses of trypsin did not decrease lipase activity. Conversely, the addition of a single dose of chymotrypsin after inhibiting trypsin activity markedly decreased lipase activity (P less than 0.004). In conclusion, chymotrypsin is a more potent inactivator of human lipase than trypsin; chymotrypsin inactivates lipase in the absence of trypsin, but trypsin inactivation of lipase requires chymotrypsin.
Effect of coinfusion of cholic acid and sulfated cholic acid on bile formation in rats
Authors: Yousef I. M. , Tuchweber B. , Mignault D. , Weber A.
Published: December 2017

The effect of combined infusion of sulfated cholic acid and nonsulfated cholic acid on bile formation was investigated. The data show that the secretion of sulfated cholic acid is slower and does not share the same transport mechanism(s) as nonsulfated cholic acid. Sulfated cholic acid significantly increased bile flow and reduced the secretion of biliary phospholipids, cholesterol, and protein associated with the secretion of exogenous nonsulfated cholic acid, only when they were infused in a ratio higher than 2:1 (sulfated:nonsulfated). Thus it is concluded that sulfated bile acids may protect the liver against the toxic effect of high concentration of bile acids. The relevance of these findings to human cholestasis remains to be determined because sulfated bile acids do not predominate in serum during cholestasis.
Are relaxation oscillators an appropriate model of gastrointestinal electrical activity?
Authors: Publicover N. G. , Sanders K. M.
Published: December 2017

Mathematical models based on relaxation oscillators have heavily influenced the terminology and experimental designs of investigations in gastrointestinal motility for nearly two decades. Relaxation oscillator equations have been used to stimulate the electrical activities of the esophagus, stomach, small intestine, colon, and rectosigmoid region. It has been suggested that many attributes of gastrointestinal electrical activity cannot be adequately explained by classic "core-conductor" or "cable" models of excitation and conduction. This article critically reviews the relaxation oscillator model and provides an explanation for each of the putative inadequacies of core-conductor theory. Furthermore, we question whether relaxation oscillator equations are able to simulate the waveforms of gastrointestinal slow waves, alterations in waveform in response to drugs or electrical stimulation, patterns of slow-wave activity when stimulated at physiological frequencies, prolonged periods of constant resting membrane potential between gastric slow waves and electrotonic spread into inactive regions. We conclude that the relaxation oscillator equations do not fully describe gastrointestinal electrical activity; excitation and propagation can be modeled by a theory that provides for morphological features, ionic conductances, and other elements included in the cable equations.
Postprandial gastrointestinal blood flow and oxygen consumption during environmental cold stress
Authors: Mayfield S. R. , Oh W. , Piva D. L. , Stonestreet B. S.
Published: December 2017

We studied the independent and combined effects of feeding and environmental cold stress by measuring pre- and postprandial gastrointestinal blood flow (QGI), oxygen consumption (GIVO2), and oxygen extraction (GIO2ex) in seven awake 3- to 4-day-old piglets while in a thermoneutral environment (control phase, 31 degrees C) and during environmental cold stress (experimental phase, 20.5 degrees C). Each animal consecutively completed both the control and experimental phases. In the control phase, measurements were made before and 30 min after feeding. In the experimental phase, measurements were made before and 30 min after induction of cold stress. A feeding was then given and measurements repeated 30 min later during continued cold stress. QGI (ml.100 g-1.min-1) increased postprandially while in a thermoneutral environment (130 +/- 11 to 152 +/- 12) but not while in a cold environment (126 +/- 15 to 121 +/- 8). Postprandial GIVO2 (ml O2.100 g-1.min-1) increased from 2.1 +/- 0.2 to 3.7 +/- 0.5 while in a warm environment. During preprandial cold stress, an unexpected increase in GIVO2 was observed (1.7 +/- 0.2 to 3.1 +/- 0.5). Feeding while in a cold environment provoked a further significant increase in GIVO2 (3.1 +/- 0.5 to 4.2 +/- 0.4). All increases in GIVO2 were associated with increased GIO2ex. This study has demonstrated that 1) postprandial GIVO2 is appropriately increased during cold stress as a function of GIO2ex and 2) that fasting GIVO2 is increased during cold stress, demonstrating an intestinal metabolic contribution to cold-induced systemic thermogenesis.
Proton permeability and lipid dynamics of gastric and duodenal apical membrane vesicles
Authors: Wilkes J. M. , Ballard H. J. , Dryden D. T. , Hirst B. H.
Published: December 2017

The passive proton permeability (Pnet) of apical membrane vesicles from rabbit parietal cells (gastric) and duodenal and renal cortical brush-border membranes (BBM) was determined by acridine orange fluorescence quenching. Values of Pnet were found to be gastric (4 x 10(-4) cm/s) less than duodenal (10(-3) cm/s) much less than renal (10(-2) cm/s). Arrhenius plots of the temperature profile of proton permeation of gastric vesicles was linear, whereas that of duodenal BBM displayed a discontinuity at 30-33 degrees C. Alcohols (octyl, benzyl, ethyl) increased Pnet in a concentration-dependent manner, with efficacy related to their oil-water partition coefficients. In a parallel series of experiments, structural parameters of the vesicle membrane lipids (fluidity) were monitored from both the steady-state and time-resolved fluorescence anisotropy of diphenylhexatriene. Fluidity of the membranes was unrelated to Pnet (renal congruent to duodenal less than gastric). Gastric vesicles demonstrated a linear Arrhenius plot of temperature dependence for fluidity, whereas duodenal BBM demonstrated a discontinuity. Membrane fluidity of gastric and duodenal vesicles was increased by alcohols, with the same potency as for Pnet, and these two variables were significantly correlated after perturbation with alcohols. Thus the fluidity of the lipid bilayer is not the major determinant of Pnet, but alteration of its structural parameters, as reflected by fluidity, produces parallel changes in Pnet.
Differential effects of thyroxine and cortisone on jejunal sucrase expression in suckling rats
Authors: Yeh K. Y. , Yeh M. , Holt P. R.
Published: December 2017

Effects of thyroxine (T4) and cortisone (C) on developmental expression of jejunal immunoreactive sucrase-isomaltase (S-I) and sucrase activity in suckling rats were studied to determine whether these hormones have distinctive actions. Immunoreactive S-I and sucrase activity were absent in infant rats and appeared simultaneously on days 16-18, when cells expressing S-I protein were detected at the villus base. By day 22, the entire jejunal mucosal surface was covered by new cells expressing immunoreactive S-I. Jejunal S-I content surged to adult levels on day 22, whereas the sucrase activity of immunoreactive S-I protein increased continuously until day 32. Administration of 12.5 nmol of T4 or 1.25 mumol of C on day 12 induced precocious expression of jejunal sucrase activity on day 15. T4 also induced sucrase activity in adrenalectomized rats without increasing serum corticosterone concentrations. Both T4 and C appeared to exert their effects in crypt cells, since immunoreactive S-I protein appeared only in villus base cells 24 h after administration. Pulse labeling of [14C]leucine showed that both hormones evoked de novo synthesis of S-I. The S-I induced by C had significantly higher sucrase activity than that induced by T4. We conclude that postnatal development of sucrase activity results from de novo synthesis of S-I with progressively higher catalytic activity until day 32 and these developmental processes are sequentially modulated by thyroid and adrenocortical hormones.
Mucosal ornithine decarboxylase in the small intestine: localization and stimulation
Authors: Johnson L. R. , Tseng C. C. , Wang P. , Tipnis U. R. , Haddox M. K.
Published: December 2017

In most tissues increases in ornithine decarboxylase (ODC) are associated with growth. Refeeding fasted rats. a potent stimulus for mucosal growth, strongly increases ODC in both small and large intestinal mucosa. In the small bowel, almost all of this increase occurs in the mature villus cells rather than the proliferative crypt cells. Nevertheless, inhibition of ODC with difluoromethylornithine blocks the growth response. Using a highly specific, polyclonal antiserum to ODC, we have determined that in the fasted rat ODC is localized almost exclusively to the villus cells. Using antiserum dilution techniques, we have shown that, within 2 h, refeeding increases the amount of immunoreactive ODC in both villus and crypt cells. Furthermore, the trophic hormone gastrin also increases ODC, but only in the crypt cells. Epidermal growth factor increased ODC to a greater extent than gastrin, but stimulation was more general, including both crypt and villus cells. Perfusing an isolated segment of small bowel in situ with glycine for 2 h also increased immunoreactive ODC but only in the villus cells. Thus in the small intestine the effect of refeeding on ODC activity appears to be mediated by different types of stimuli: luminal nutrients increase enzyme levels in the absorbing villus cells, while trophic peptides stimulate ODC synthesis in the proliferative crypt cells.
Eicosanoid interactions in the canine proximal colon
Authors: Keenan C. M. , Rangachari P. K.
Published: December 2017

Effects of eicosanoids on the canine proximal colonic mucosa were examined. Both arachidonic acid (AA) and prostaglandin E2 (PGE2) increased short-circuit currents. Tetrodotoxin did not affect these responses, suggesting that functioning nerves are not required. Indomethacin abolished responses to AA, indicating that the cyclooxygenase pathway is the primary metabolic pathway. Indomethacin significantly potentiated responses to PGE2, suggesting that in the presence of cyclooxygenase inhibition either 1) a normally inhibitory cyclooxygenase product is not present or 2) a potentiating lipoxygenase product is being produced in greater amounts. PGE2 is produced in significant quantities, whereas leukotriene B4 (LTB4) is produced in smaller amounts. Cyclooxygenase inhibitors significantly decreased PGE2 production but had no effect on LTB4. This suggests that an inhibitory PG may be opposing the response to PGE2. Therefore, we tested the effects of several cyclooxygenase products on PGE2 responsiveness. PGD2 alone significantly reduced responses to PGE2. In the canine proximal colon the response to AA is apparently the algebraic sum of the opposing responses of PGE2 and PGD2.
Effect of purified Clostridium difficile toxins on intestinal smooth muscle. I. Toxin A
Authors: Gilbert R. J. , Triadafilopoulos G. , Pothoulakis C. , Giampaolo C. , LaMont J. T.
Published: December 2017

In these studies we determined the effects of purified Clostridium difficile toxin A, an enterotoxin, on the electrophysiological and contractile properties of rabbit intestinal circular smooth muscle and correlated these effects with changes of smooth muscle morphology. Simultaneous measurements of intracellular membrane potential and contractility were determined in excised ileal muscle strips after administration of toxin A in vivo (60 micrograms/ml) into an isolated rabbit ileal loop or directly in vitro (0.1-60 micrograms/ml) to a normal muscle strip. Toxin A injection in vivo resulted in membrane depolarization and increased slow wave and action potential frequency. Toxin A injection in vivo also caused increased amplitude of spontaneous and carbachol-induced phasic contractions. The electrophysiological effects of in vivo administration of toxin A were correlated with an inflammatory infiltrate of the lamina propria, but no light or electron microscopic evidence of injury to smooth muscle cells was seen. In contrast to the in vivo studies, direct in vitro exposure of normal ileal muscle strips to toxin A had no effect on either spontaneous or carbachol-induced electromechanical activity. Our results indicate that in vivo administration of C. difficile toxin A into a rabbit ileal loop, but not direct in vitro exposure, causes significant alterations of smooth muscle excitation-contraction coupling that may be mediated by products of local inflammatory cells.
Effect of purified Clostridium difficile toxins on intestinal smooth muscle. II. Toxin B
Authors: Gilbert R. J. , Pothoulakis C. , LaMont J. T.
Published: December 2017

In the companion paper [Am. J. Physiol. 256 (Gastrointest. Liver Physiol. 19): G759-G766, 1989] we showed that highly purified Clostridium difficile toxin A had a profound effect on intestinal smooth muscle after in vivo but not in vitro exposure. In this study we assessed the effects of in vivo and in vitro exposure to C. difficile toxin B on simultaneous measurements of intracellular membrane potential and contractility in rabbit ileal smooth muscle. Direct exposure of ileal smooth muscle to toxin B (0.1-60 micrograms/ml) in vitro caused membrane depolarization and inhibition of action potential frequency, amplitude, and peak voltage, but no effect on slow wave frequency or amplitude was seen. Toxin exposure also resulted in inhibition of the amplitude of carbachol-induced contractions, with phasic contractions being significantly more sensitive to the effect of toxin B than tonic contractions over the complete dose range. The electromechanical effects of toxin B were not affected by prior administration of tetrodotoxin, atropine, hexamethonium, or phentolamine. In contrast, toxin B administered in vivo into an isolated ileal loop had no effect on spontaneous electromechanical properties of excised smooth muscle strips. Our results indicate that direct exposure in vitro of ileal smooth muscle to C. difficile toxin B causes membrane depolarization in association with inhibition of electromechanical activity. This effect, in combination with the indirect effects of toxin A, may contribute to altered intestinal motility during diarrhea caused by C. difficile.
Modulation of the duration of human postprandial motor activity by sleep
Authors: Kumar D. , Soffer E. E. , Wingate D. L. , Britto J. , Das-Gupta A. , Mridha K.
Published: December 2017

We have measured the effect of the presence of food in the gastrointestinal tract on proximal small bowel motility during sleep. Motility was measured in eight healthy ambulant subjects using two strain-gauge microtransducers incorporated in a fine (2.5 mm OD) nasojejunal tube. The subjects ate a 540-cal evening meal (EM) on the first day. On the following day they ate an equicaloric meal (with similar proportion of carbohydrates, proteins, and fats) at lunch time (MM) and then another equicaloric late meal (LM) 15 min before going to bed. All subjects were asleep within 30 min of completing the LM. Postprandial activity was significantly (P less than 0.001) shortened after LM, but there was no difference in the postprandial motor activity after MM and EM. Migrating motor complex (MMC) cycle lengths were similar after MM, EM, and LM. There was no difference in the duration of phase II of the MMC cycle after MM, EM, and LM even though subjects were asleep during the MMC cycles after LM. The MMC propagation velocity after LM and EM was significantly (P less than 0.01, P less than 0.001, respectively) slower than the diurnal MMC propagation velocity after MM. In health, postprandial activity is diminished during sleep, whereas the consumption of a LM restores the phase II activity usually absent during sleep. A LM also abolishes the expected reduction in nocturnal MMC cycle length but maintains the circadian variation in the propagation velocity of the MMC cycle.
Transport of beta-lactoglobulin across rabbit ileum in vitro
Authors: Marcon-Genty D. , Tome D. , Kheroua O. , Dumontier A. M. , Heyman M. , Desjeux J. F.
Published: December 2017

Intestinal transepithelial transport constitutes a major limiting step in the transfer of food protein antigens to the blood. This transport was studied in isolated rabbit ileum in Ussing chamber in vitro for the milk protein antigen beta-lactoglobulin (beta-Lg). The transepithelial passage of beta-Lg was measured by enzyme-linked immunosorbent assay (ELISA) and radiolabeled protein transfer and compared with that of the nonmetabolizable marker polyethylene glycol (PEG)-4000. When 1 mg/ml of beta-[14C]Lg or [3H]PEG was added to the mucosal side of the tissue, the total uptake, measured as the transfer of radiolabeled material across the ileum, was significantly higher for beta-Lg than for PEG (5.46 +/- 1.75 vs. 1.43 +/- 0.26 micrograms.h-1.cm-2). Measured by ELISA, 6-9% of the total amount of beta-Lg transported was absorbed in an intact antigenic form. This transport of intact beta-Lg was inhibited by the metabolic inhibitors 50 mM 2-deoxyglucose and 1 mM azide added simultaneously, was reduced by the microtubule assembly inhibitor 0.05 mM colchicine, and was enhanced by 20 mM ammonia, which inhibits lysosomal proteolytic activity. These results indicate that beta-Lg is efficiently absorbed by the intestinal mucosa of adult animals, partly in intact antigenic form and that beta-Lg transport is probably transcellular, as observed for other proteins. The finding that beta-Lg is absorbed in intact antigenic form agrees with other reports implying that beta-Lg is the main factor responsible for milk protein immunoreactivity and intolerance.
Gastric acid secretion and parietal cell mass: effects of thyroidectomy and thyroxine
Authors: Adeniyi K. O. , Olowookorun M. O.
Published: December 2017

The role of thyroid hormones on parietal cell function and number was studied in the rat. Chronic administration of thyroxine (6-8 micrograms/100 g body wt/day) for 35 days significantly increased parietal cell mass (from 21.18 +/- 0.13 x 10(6) to 26.71 +/- 0.14 x 10(6] as well as basal acid secretion (from 3.69 +/- 0.08 to 4.99 +/- 0.16 mueq/10 min) and histamine-stimulated acid secretion (from 2.45 +/- 0.12 to 3.69 +/- 0.21 mueq/10 min). Thyroidectomy decreased the number of parietal cells in the gastric mucosa (to 10.48 +/- 0.09 x 10(6] and basal acid secretion (to 3.09 +/- 0.08 mueq/10 min). Histamine (0.2 mg) injection into the thyroidectomized rats increased acid secretion by only 1.41 +/- 0.06 mueq/10 min as against 2.45 +/- 0.12 mueq/10 min obtained for control rats. The results suggest that thyroid hormones regulate basal and secretagogue-stimulated acid secretion via their effects on parietal cell mass.