bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous reflex inhibition of lower esophageal sphincter and crural diaphragm in cats
Authors: Altschuler S. M. , Boyle J. T. , Nixon T. E. , Pack A. I. , Cohen S.
Published: December 2017

We have previously suggested that both the lower esophageal sphincter and diaphragm contribute to the high-pressure zone (HPZ) at the gastroesophageal junction. The purpose of this study in anesthetized cats was to compare changes in diaphragmatic electrical activity with changes in the intraluminal pressure profile in the HPZ following either balloon distension of the esophagus or swallowing evoked by pharyngeal stimulation. Intraluminal pressure was continuously recorded by a perfused manometric assembly anchored to the gastric fundus through an abdominal surgical approach. Integrated EMG was simultaneously measured in the costal and crural parts of the diaphragm. Our results indicate that simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm follows both swallowing and balloon distension of the esophagus; during swallowing both inhibitory reflexes depend on the initiation of esophageal peristalsis; crural relaxation abolishes respiratory-induced pressure oscillations in the HPZ during LES relaxation; ventilation is maintained during relaxation of the HPZ in part by continued contraction of the costal diaphragm; and different neural pathways control LES relaxation and crural relaxation. The data support the view that the crural diaphragm augments the intrinsic smooth muscle sphincter mechanism at the gastroesophageal junction and that crural relaxation may be an important factor in mouth-to-gastric transit.
Vagal control of fluid transport, transmural potential difference, and motility in the ferret jejunum
Authors: Greenwood B. , Read N. W.
Published: December 2017

The role of the vagus nerve in the control of intestinal transport was investigated in the ferret jejunum in vivo. Fluid transport was measured in an isolated 10-cm segment of jejunum by means of a single-pass perfusion technique with radioactive markers introduced into the perfusion fluid and the bloodstream of the animal. Transmural potential difference (PD) and intraluminal pressure in the perfused jejunal loop were also monitored. Vagal stimulation (20 Hz, 20 V, and 0.5 ms for 1 min) resulted in jejunal fluid movement in the direction of secretion, a rise in transmural PD, and an increase in jejunal contractile activity. Similar changes were induced by close intra-arterial injection of acetylcholine (20 micrograms X kg-1). The contractile response to vagal stimulation was abolished by atropine. Moreover, atropine did not block the changes in fluid transport and transmural PD that were induced by vagal stimulation, although the transmural PD response was reduced. The results suggest that vagal stimulation induces intestinal secretion accompanied by a rise in transmural PD; the events are mediated at least in part by a noncholinergic transmitter as yet undetermined.
Organization of fasting and postprandial myoelectric activity in stomach and duodenum of conscious dogs
Authors: Gill R. C. , Pilot M. A. , Thomas P. A. , Wingate D. L.
Published: December 2017

In conscious dogs, contractile and myoelectric activity was recorded from force transducers and monopolar electrodes chronically implanted in the serosal surface of the proximal and distal stomach. Periodic activity during fasting was characterized at each site. Proximally, activity fronts consisted of a series of regular large-amplitude contractions, without correlated myoelectric changes, occurring at 50-s intervals. The distal activity front comprised a series of bursts of two to three contractions 11 s apart, with each burst in phase with a proximal contraction. Only during the burst sequence was each electrical slow wave associated with a spike burst (1:1 phase locking). In contrast, 1:1 phase locking characterized the electrical correlates of the duodenal activity front. Oral feeding abolished periodic activity for at least 3 h. Postprandially, the proximal stomach remained electrically silent; in the duodenum spike bursts were intermittently associated with regular slow waves, but in the distal stomach regular low-amplitude contractions were characterized electrically by 1:1 phase-locked spike bursts and slow waves. These observations suggest that the proximal stomach regulates the canine fasting activity front and require modification of the concept that 1:1 phase locking is a necessary condition of the activity front.
In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein
Authors: Saluja A. , Saito I. , Saluja M. , Houlihan M. J. , Powers R. E. , Meldolesi J. , Steer M.
Published: December 2017

Infusion of a supramaximal dose of caerulein results in acute interstitial pancreatitis in rats. We report studies of in vivo pancreatic acinar cell function during the initial 3.5 h of supramaximal stimulation with caerulein (5 micrograms X kg-1 X h-1). Amino acid [( 3H]phenylalanine) uptake was not altered, and there was no change in the rate or extent of protein synthesis or in intracellular transport of in vivo pulse-labeled proteins from microsome to zymogen granule-enriched fractions. However, the discharge of labeled protein was markedly inhibited. Radioautographic studies indicated that the pulse-labeled proteins retained in the gland were not located extracellularly but had accumulated within acinar cells, with a preferential distribution at the cell apex (presumably in zymogen granules) and in large vacuoles that form within the cell during hyperstimulation. Supramaximal stimulation with caerulein also caused increasing amounts of amylase and labeled proteins to be recovered in the postmicrosomal fraction. These findings suggest that supramaximal stimulation causes digestive enzymes to become localized in organelles that are fragile and subject to disruption during tissue homogenization. These organelles may be the vacuoles noted in morphological studies and believed to represent immature condensing vacuoles and/or crinophagic vacuoles.
D-Glucose transport in piglet jejunal brush-border membranes: insights from a disease model
Authors: Keljo D. J. , MacLeod R. J. , Perdue M. H. , Butler D. G. , Hamilton J. R.
Published: December 2017

We measured glucose transport in jejunal brush-border membrane vesicles isolated from piglets with acute viral diarrhea, comparing our results with those from control animals. Characterization of membranes from both study groups demonstrated comparable purity and integrity. In the presence of an inwardly directed Na SCN gradient, D-glucose accumulated in control vesicles to a concentration several times the 60-min equilibrium level. "Overshooting" uptake was much lower and more gradual in vesicles from 40-h transmissible gastroenteritis (TGE)-infected pigs compared with control pigs. Equilibrium kinetic studies, in which gramicidin was used to clamp membrane potential at zero, demonstrated a pattern of Na-dependent D-glucose transport in 40-h TGE-infected membranes that differed greatly from the control pattern. From an Eadie-Hofstee plot of stereospecific Na-dependent D-glucose uptake into control vesicles, a pattern suggesting two carrier populations emerged: one with a low-affinity, apparent Km equaling 52.63 +/- 13.81 mM and the other a high-affinity apparent Km equaling 3.92 +/- 0.24 mM for D-glucose. In 40-h TGE-infected membranes, the pattern conformed to a single line, suggesting a homogeneous population of low-affinity carriers, (Km = 37.03 +/- 1.92 mM), which did not differ from the low-affinity carriers seen in control animals. We conclude that the absence of the high-affinity D-glucose carriers in jejunal brush-border membrane is an important determinant of the defective glucose transport that characterizes viral diarrhea. Because previous studies have strongly suggested that in acute TGE diarrhea the epithelium is composed of relatively undifferentiated crypt-type cells, we speculate that high-affinity D-glucose carriers are lacking in normal crypt epithelial cells and that they are incorporated into brush-border membranes of jejunal enterocytes as the cells differentiate in the course of their migration from crypt to villus.
Effect of sugars and amino acids on amphibian intestinal Cl- transport and intracellular Na+, K+, and Cl- activity
Authors: White J. F. , Burnup K. , Ellingsen D.
Published: December 2017

The effect of glucose, galactose, and valine on intestinal Cl- transport and intracellular Cl-, Na+, and K+ activity was investigated in isolated segments of Amphiuma small intestine. By use of double-barreled Cl- -specific microelectrodes, it was observed that galactose and valine reduced the luminal membrane potential (psi m) and eliminated the difference between the Cl- equilibrium potential (ECl) and psi m, i.e., the Cl- accumulation potential (ECl-psi m) approached zero. Simultaneously, Cl- absorption (JnetCl) was reduced in short-circuited tissues and Na+ absorption was enhanced. In contrast, after exposure to glucose, psi m and ECl-psi m declined only transiently and JnetCl was unaltered. In tissues pretreated with galactose to reduce Cl- transport, addition of glucose to the serosal medium restored Cl- accumulation across the luminal membrane and the Cl- absorptive current. Glucose, galactose, and valine each reduced intracellular K+ activity significantly. Galactose and valine each increased [corrected] intracellular Na activity (aiNa) markedly, whereas glucose increased aiNa only slightly. In conclusion, intestinal ion transport can be limited by the availability of metabolic substrate. The nonmetabolized solutes galactose and valine inhibited Cl- uptake and net Cl- absorption while stimulating net Na absorption, as though net Na+ absorption has priority over Cl- transport at the cellular level. Cl- transport is reduced at both mucosal and serosal membranes. At the luminal membrane electrogenic Cl- uptake is slowed or a backleak of Cl- is enhanced; at the serosal membrane Cl- exchange with Na+ (and HCO3-) driven by the Na+ gradient is reduced. The availability of metabolizable glucose to the cell prevents the reduction in net Cl- absorption.
Chloride transport of frog gastric fundus: effects of omeprazole
Authors: Starlinger M. J. , Hollands M. J. , Rowe P. H. , Matthews J. B. , Silen W.
Published: December 2017

Omeprazole (10(-4) M) inhibited H+ secretion and increased potential difference (PD), resistance, and short-circuit current (Isc) in chambered bullfrog gastric mucosa, but the electrical changes developed only in tissues previously exposed to histamine. Net chloride transport (JnetCl) did not change after omeprazole under short-circuited conditions, and Isc increased to become equal to JnetCl. Under open-circuit conditions, JnetCl was reduced by 38%, the decrement attributable to the concomitant increase in PD, as evidenced by a linear relationship between JnetCl and PD in omeprazole-treated mucosae clamped to different PD (0-45 mV). The effect of omeprazole on PD and Isc could be blocked by metiamide and was absent in spontaneously resting tissues. HEPES nutrient solutions did not alter the electrical response or Cl- transport after omeprazole. In Na+-free solutions, omeprazole induced only a transient rise in PD and Isc. We conclude that omeprazole uncouples H+ and Cl- secretion. This Cl- secretion is electrogenic and dependent upon stimulation by histamine. Both Na+ and HCO3- seem to be involved in movement of Cl- across the basolateral membrane.
Electrogastrographic characteristics of interdigestive migrating complex in humans
Authors: Geldof H. , van der Schee E. J. , Grashuis J. L.
Published: December 2017

Interdigestive myoelectric activity and mechanical activity were studied simultaneously by means of cutaneous electrodes (electrogastrography) and intraluminal pressure recording, respectively, in 10 healthy male volunteers. The aims of the present study were 1) to describe the characteristics of the electrogastrogram during the different phases of the interdigestive migrating complex (IMC) in healthy subjects and 2) to determine to what extent these characteristics can be used to identify the different phases of the IMC. The electrogastrograms were analyzed visually and by running-spectrum analysis. It was concluded that in humans the gastric frequency present in the electrogastrogram appears to be less stable during motor activity than during motor quiescence, in particular during phase III, but far more stable than its canine counterpart. A small but consistent drop in gastric frequency was observed in the changeover from motor quiescence to phase II motor activity. The power of the gastric frequency increased with increasing motor activity, except during phase III. A characteristic frequency and power behavior during phase III could only be recognized in a minority of the IMCs. In general, electrogastrography cannot, given the present state of the art, be used to precisely identify the different phases of the IMC.
Postnatal maturation of enterocytes in sparse-fur mutant mice
Authors: Malo C. , Qureshi I. A. , Letarte J.
Published: December 2017

In adult sparse-fur mutant mice, ornithine transcarbamylase (OTC) activity represents only 14% of the normal values. We studied the development of this activity from birth to adult period and demonstrated that the enzyme deficiency is already fully expressed at birth, in both the liver and the small intestine of mutants. Since OTC catalyzes the conversion of ornithine to citrulline, in the presence of carbamoyl-phosphate, the effect of a disturbed ornithine metabolism on the postnatal development of the small intestine has been evaluated. The normal appearance of sucrase as well as the normal increase of glucoamylase, trehalase, and alkaline phosphatase activities are delayed in sparse-fur mice compared with controls. Moreover, normal adult values are never attained. In contrast, the normal decline of lactase activity is impaired while leucylnaphthylamidase activity is unaffected. Cell proliferation, as evaluated by [3H]thymidine incorporation into DNA and mitotic index, is less active during the 3rd wk of life in mutants. These phenomena are closely associated with a transient weak arginase and ornithine decarboxylase activity in the small intestine. Since arginase catalyzes the conversion of arginine to orthithine, thus ensuring the availability of this substrate for ornithine decarboxylase activity, these results indicate a disturbance of polyamine metabolism in mutant enterocytes with a consequent delay in postnatal differentiation and proliferation. Sparse-fur mutant mouse may therefore represent a useful animal model for evaluating the role of ornithine metabolism in the maturation process of the small intestine.
Gastric motility is a major factor in cold restraint-induced lesion formation in rats
Authors: Garrick T. , Buack S. , Bass P.
Published: December 2017

These studies were performed to characterize the pattern of gastric contractility associated with cold restraint-induced lesion formation. Gastric motility in the rat was examined with extraluminal transducers at three sites of the stomach. The motility was monitored in the 24-h-fasted state, the postprandial state, and during cold-water immersion restraint. Gastric acid secretion was also monitored in a separate group of animals placed in cold restraint. Both feeding and cold restraint resulted in an equivalent increase in the amplitude of gastric contractions. Prolonged cold restraint, however, resulted in a distinct contractile pattern in which contractions were 56% less frequent and 300-400% longer in duration than those stimulated by feeding. All cold-restrained animals developed multiple gastric erosions. Cold restraint was not associated with increased acid secretion. A single subcutaneous injection of papaverine HCl (50 or 100 mg/kg) suppressed cold restraint-induced high-amplitude contractions and the cold restraint-induced lesion formation without altering acid secretion. These studies suggest that the stimulation of high-amplitude, prolonged duration contractions are more important than changes in gastric acid secretion in the formation of cold restraint-induced gastric lesions.
Ontogeny of pepsin secretory response to secretagogues in isolated rat gastric glands
Authors: Yahav J. , Lee P. C. , Lebenthal E.
Published: December 2017

By use of isolated gastric glands from rats at various ages, we demonstrated that full-term neonate and 1-day-old rats showed no response to cholecystokinin octapeptide (CCK-OP), carbachol, or Ca2+ ionophore. The same glands, however, were responsive to dibutyryl cAMP. A mature response was not found until the pups were 2 days old. Injection of hydrocortisone into newborn rats led to an increase in pepsinogen concentrations in gastric glands and also an increased responsiveness to CCK-OP, carbachol, and Ca2+ ionophore A23187 24 h after administration. Hydrocortisone thus caused precocious maturation of both pepsinogen accumulation and pepsinogen secretory responsiveness of gastric glands in rat pups.
Kinetics of glutathione efflux from isolated rat hepatocytes
Authors: Aw T. Y. , Ookhtens M. , Ren C. , Kaplowitz N.
Published: December 2017

The characteristics and kinetics of glutathione (GSH) efflux were examined in homogeneous suspensions of freshly isolated rat hepatocytes. GSH efflux was measured as its linear accumulation in the suspension medium. Appearance of GSH extracellularly was reflected in a quantitative loss in cellular GSH. However, the total GSH remained essentially unchanged, indicating minimal net synthesis of GSH under these experimental conditions. GSH efflux was sensitive to temperature, with a calculated Q10 value of 2.3. A wide range of cellular GSH concentration ranging from near complete and moderate depletion to severalfold the control values was achieved by treatment of animals or cells with various GSH depletors or inducers. At physiological (fed) and elevated (3-methylcholanthrene- and CoCl2-induced) cellular GSH, the rate of GSH efflux was near maximum. The rate fell dramatically to 50% maximum at a GSH concentration equaling 35 nmol/10(6) cells. A 48-h fast resulted in a 40% loss of cellular GSH, with a corresponding decrease in efflux rates. Addition of GSH to the incubation medium had no effect on efflux rates. The relationship of GSH efflux to cellular GSH concentration was characterized by apparent sigmoidal saturation kinetics. The data were fitted well by the Hill model with the following kinetic parameters: Vmax = 0.25 nmol X 10(6) cells-1 X min-1, Km = 3.5 mM, and n = 3. These results correspond very closely to our previous findings in the perfused liver.
Histamine H2-receptor involvement in the regulation of gastric emptying
Authors: Dubois A. , Castell D. O.
Published: December 2017

The effect of cimetidine on gastric emptying and gastric secretion was evaluated in eight chair-adapted rhesus monkeys. A dye-dilution technique was used to simultaneously determine gastric emptying, gastric secretion of water and hydrogen ion (H+), and intragastric volume and H+ concentration. A continuous intravenous infusion of either saline (control) or cimetidine (4 mg X kg-1 X h-1) was administered during a 40-min fasting steady state and following intragastric instillation of 100 ml of water. During fasting, administration of cimetidine abolished H+ secretion and significantly decreased fractional emptying rate and water secretion (P less than 0.05). After the water load, cimetidine also suppressed H+ secretion and reduced fractional emptying and water secretion compared with control (P less than 0.05). Increasing HCl concentration of the test solution to 50 mM significantly decreased fractional emptying both during saline and further suppressed emptying during cimetidine infusion (P less than 0.05). In conclusion, cimetidine significantly decreased gastric emptying during fasting and following a liquid load. Restoring intragastric acidity to physiological levels removed the effect of gastric acid suppression on emptying and unmasked the full potential for cimetidine to decrease gastric emptying, possibily through an effect on gastric smooth muscle.
Anamnestic stimulus-specific myoelectric responses associated with intestinal immunity in the rat
Authors: Palmer J. M. , Castro G. A.
Published: December 2017

Changes in small intestinal motility reflective of local anaphylaxis are hypothesized to be associated with the rapid, immune-mediated rejection of infective larvae of the nematode Trichinella spiralis. This hypothesis was tested by comparing intestinal myoelectric activity in primarily and secondarily infected rats; the latter group represented immunized hosts, i.e., immunized by initial contact with the parasite. Patterns of slow waves, action potentials, interdigestive migrating myoelectric complexes, and migrating action-potential complexes induced by secondary infection differed from those associated with primary infection. Patterns in both cases differed from those in uninfected rats. Secondary but not primary infection evoked changes in myoelectric patterns within 15 min after administration of infective larvae. These changes could not be elicited by inoculation with dead larvae, larval excretory-secretory antigens, or a heterologous parasite, Eimeria nieschulzi. Results indicate that altered smooth muscle contractile activity is part of an anamnestic, stimulus-specific response to T. spiralis in immunized rats. These changes may represent the in vivo equivalent of the anaphylactically mediated intestinal smooth muscle contraction elicited in vitro in the Schultz-Dale reaction.
Sodium-dependent transport of Pi by an established intestinal epithelial cell line (CaCo-2)
Authors: Mohrmann I. , Mohrmann M. , Biber J. , Murer H.
Published: December 2017

The uptake of inorganic phosphate (Pi) was analyzed in monolayers and in apical membrane vesicles (AMV) of the established intestinal cell line CaCo-2. AMV, prepared by a MgCl2 precipitation technique, were enriched approximately 10-fold in alkaline phosphatase activity. Pi uptake into intact cells as well as into AMV was specifically dependent on the presence of sodium. In the presence of high sodium concentrations, the apparent Km for Pi was 214 +/- 17 mumol/l in monolayers and 300 +/- 19.7 mumol/l in AMV. Increasing the sodium concentration increased the apparent affinity of the transport system for Pi but hardly affected the maximal velocity (Vmax). At 0.1 mmol/l Pi and pH 7.4, the apparent Km for sodium was approximately 70 mmol/l in intact cells as well as in AMV. The results obtained in both systems suggested the involvement of two sodium ions and one phosphate ion in the transport process. Advancing confluence--independently of the age of the monolayers--reduced sodium-dependent uptake of Pi significantly by a decrease in Vmax, whereas the apparent Km for Pi remained unchanged. It is concluded that the apical membrane of CaCo-2 cells contains a sodium-dependent transport system for Pi.
Hepatic processing of cholecystokinin peptides. I. Structural specificity and mechanism of hepatic extraction
Authors: Gores G. J. , LaRusso N. F. , Miller L. J.
Published: December 2017

Since the liver is a target tissue of many biologically important molecules, we have studied the hepatic uptake of cholecystokinin (CCK) with the isolated, perfused rat liver and a series of radioiodinated and unlabeled CCK peptides. Of the naturally occurring forms of CCK, cholecystokinin octapeptide (CCK-8) was extensively extracted (26 +/- 0.7% of Bolton-Hunter-labeled CCK-8, 59% of unlabeled CCK-8) in a single pass through the liver, while CCK-33 was minimally extracted (3.1 +/- 1.2% of Bolton-Hunter-labeled CCK-33). Studies of structural specificity showed that the sulfate ester on the tyrosine residue of CCK-8 decreased its hepatic extraction, that the carboxyl-terminal tetrapeptide region of CCK-8 was more important for this uptake process than was the amino-terminal tetrapeptide region, and that oxidation reduced uptake of CCK. First-pass hepatic extraction of unlabeled CCK-8 was shown to be a high-capacity process; however, uptake of radioiodinated CCK-8 was partially saturable with unlabeled CCK-4. Specific lectins (wheat-germ agglutinin, concanavalin A) and a bile acid (taurocholate) inhibited hepatic extraction of CCK-8 in a concentration-dependent manner. These data are consistent with a highly specific cellular extraction process for CCK in the liver.
Hepatic processing of cholecystokinin peptides. II. Cellular metabolism, transport, and biliary excretion
Authors: Gores G. J. , Miller L. J. , LaRusso N. F.
Published: December 2017

We have shown that radiolabeled cholecystokinin octapeptide (CCK-8), CCK-8-desulfate, and CCK-4 are extracted by the liver in a structurally specific manner. Thus, we studied the fate of the extracted radiolabeled peptides by quantitating biliary excretion and determining the nature of the metabolites in bile. There was rapid biliary excretion of labeled CCK-8, CCK-8-desulfate, and CCK-4 by the isolated, perfused rat liver; greater than 75% of the extracted dose and greater than 20% of the injected dose appeared in bile within 20 min after a single pass across the liver. By means of high-performance liquid chromatography and immunoprecipitation, we showed that CCK-8-desulfate and CCK-4 appeared in bile in completely metabolized forms. In contrast, for CCK-8, approximately 20% of the major forms of the label in bile was intact labeled octapeptide. To gain insight into the subcellular sites of metabolism and transhepatic transport of CCK-8, we also determined the effects of taurocholate, lysosomotropic agents, and microtubule binding agents on biliary excretion. Taurocholate had no effect on the percentage of the extracted label excreted into bile. Neither the percentage of the extracted label excreted into bile. Neither lysosmotropic agent, leupeptin, nor chloroquine affected the percentage of the extracted label or the nature of the metabolites appearing in bile. Two microtubule binding agents, vinblastine and colchicine, also did not affect the percentage of the extracted label appearing in bile.(ABSTRACT TRUNCATED AT 250 WORDS)
Physiological role and localization of cholecystokinin release in dogs
Authors: Konturek S. J. , Tasler J. , Bilski J. , de Jong A. J. , Jansen J. B. , Lamers C. B.
Published: December 2017

In dogs with pancreatic fistulas, meat feeding and intestinal perfusion with a sodium oleate or amino acid mixture increased pancreatic protein secretion to approximately 110, 100, and 50%, respectively, of the response to cholecystokinin (CCK) at a dose of 85 pmol X kg-1 X h-1. Plasma CCK response increased in these studies to approximately 100, 180, and 40%, respectively, of the value obtained with exogenous CCK, suggesting that, in addition to CCK, other neurohormonal factors contribute to pancreatic enzyme secretion in response to endogenous stimulants. Feeding and duodenal oleate or amino acids also stimulate the release of pancreatic polypeptide (PP), which may be involved in the control of pancreatic secretion in response to endogenous stimulants, including CCK. Perfusion of the intact intestine with graded amounts of oleate (0.5-16 mmol/h) produced dose-dependent increments in plasma CCK and pancreatic protein similar to those obtained with intravenous infusion of graded doses of CCK (0.85-255 pmol X kg-1 X h-1). Oleate perfusion of isolated Thiry loops (30 cm long) made of duodenojejunal (D-J) and ileal (I) segments also stimulated protein secretion but elevated plasma CCK only after perfusion of the D-J but not of the I loop. We conclude that 1) the endogenous CCK released by various luminal stimulants drives the pancreatic protein secretion; 2) the release of CCK is confined to the foregut; and 3) PP concomitantly released by various intestinal stimulants may contribute to the control of pancreatic secretion induced by endogenous CCK.
Potassium secretion by rabbit descending colon: effects of adrenergic stimuli
Authors: Smith P. L. , McCabe R. D.
Published: December 2017

Stripped rabbit distal colonic mucosa was studied in vitro in Ussing chambers to investigate the effects of adrenergic stimuli on Na+, K+, and Cl- transport. The adrenergic stimuli epinephrine and norepinephrine decrease short-circuit current in a dose-dependent manner, with a half-maximal effect at 5 X 10(-7) M and a maximal effect between 10(-5) and 10(-4) M. The effects produced by norepinephrine and epinephrine can also be elicited by the beta 1-agonist dobutamine, but not by the beta 2-agonist terbutaline or the alpha-agonist phenylephrine. In addition, the effects of adrenergic stimulation can be inhibited by the beta-antagonist propranolol but not by the muscarinic antagonist atropine, the alpha 2-antagonist yohimbine, or tetrodotoxin. The decrease in short-circuit current elicited by adrenergic stimuli is accompanied by an increase in net K+ secretion with no change in net Cl- or Na+ transport. This increase in net K+ secretion elicited by beta-adrenergic stimulation can be inhibited by trifluoperazine but not by indomethacin. These studies suggest that K+ transport by the colon can be regulated by adrenergic agents acting via beta 1-receptors.
Transport of butyric acid in vascularly perfused anuran small intestine: importance of pH and anion transport
Authors: Hollander D. , Gerard E. M. , Boyd C. A.
Published: December 2017

Butyric acid transport was studied in the isolated, vascularly perfused frog small intestine. At luminal butyric acid concentrations of 5-50 mM, absorption was a nonlinear function of the luminal concentration, whereas the relationship of absorption to concentration remained linear at 0-1,000 microM. The most important factor regulating the rate and direction of butyric acid transport was the pH. We used unidirectional flux analysis to determine net transport across the epithelium while the pH of the luminal or vascular compartments was changed. We found a four- to fivefold decrease in butyric acid transport into the portal circulation as the lumen pH was increased from 6.0 to 8.0. The pH of the vascular perfusate influenced the vascular-to-lumen transport of butyric acid in the same proportions. The second important regulatory factor of butyric acid transport was the 4,4'-diisothiocyananostilbene-2,2'-disulfonic acid (DIDS)-sensitive anion transport protein. DIDS added to the lumen at 10(-6) M decreased butyric acid transport by approximately 40% at pH 7.4. DIDS also inhibited butyric acid transport when added to the vascular perfusate or when transport was measured in a vascular-to-lumen direction. We suggest that, at the relatively low pH of the proximal small intestine, butyric acid becomes protonated and lipophilic and is mainly transported directly through the cell membrane. At the more alkaline pH of the distal small intestine butyric acid is in the ionized form and transport by the DIDS-sensitive anion transport protein may predominate.
Effects of NaSCN and omeprazole on resistance and potential of fundus of Rana pipiens
Authors: Rehm W. S. , Carrasquer G. , Schwartz M.
Published: December 2017

Thiocyanate (SCN) produced a rapid inhibition of acid secretion and a concurrent rapid increase in the transmucosal potential difference (PD) and resistance. After inhibition, resistance rapidly peaked and then decreased. In contrast, omeprazole produced a slow inhibition of secretion and a slow increase in PD and resistance. The peak increase in resistance with SCN was significantly greater than the steady-state increases for both SCN and omeprazole. All increases were significant. The increases in PD and resistance are greater at high H+ rates than at low H+ rates. We postulate that the peak SCN increase in resistance is due to the increase in resistance of the secretory membrane, which is followed by a decrease in resistance of the nutrient membrane. On this basis the omeprazole increase in resistance that occurs concurrently with the slow decrease in the H+ rate is a result of a concurrent change of the resistances of the two opposing membranes.
Chronic portal hypertension: effects on gastrointestinal blood flow distribution
Authors: Benoit J. N. , Womack W. A. , Korthuis R. J. , Wilborn W. H. , Granger D. N.
Published: December 2017

The intramural distribution of blood flow in the gastrointestinal tract was measured in shamoperated control and portal vein-stenosed rats. Total organ blood flow, measured via the radioactive microsphere technique, was elevated in the esophagus (66%), stomach (102%), duodenum (42%), jejunum (52%), ileum (54%), and colon (79%) of portal-hypertensive rats. Histological evaluation of carbonized nonradioactive 15-microns microspheres allowed for fractionation of blood flow within the wall (mucosa, submucosa, and muscularis externa) of each organ. The microsphere distribution pattern indicates that intramural blood flow distribution in all organs was not dramatically affected by chronic portal hypertension. These findings further define the characteristics of the factors responsible for the gastrointestinal hyperemia produced by chronic portal hypertension.
Pentagastrin on neurotransmitter enzyme activities in the rat gastrointestinal tract
Authors: Heitkemper M. M. , Shaver J. F.
Published: December 2017

The effects of three doses (5, 100, and 250 micrograms/kg) of pentagastrin on the activities of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE), the neurotransmitter enzymes that synthesize and degrade acetylcholine, and monoamine oxidase (MAO), the degradation enzyme for catecholamines, were investigated. Enzyme activities were assayed in 6 gastrointestinal segments of 21- and 28-day-old and adult rats. All animals were injected intraperitoneally for 7 days with pentagastrin, and the results were compared with age-matched controls receiving saline for 7 days. Plasma and adrenal corticosterone levels were measured. No consistent differences in adrenocortical variables existed between pentagastrin- and saline-treated animals. Similarly, no consistent pentagastrin dose responses of ChAT, AChE, and MAO activities were evident. However, at the highest dose pentagastrin generally produced increases in ChAT activities in 21- and 28-day-old rats, while producing decreases in AChE and MAO activities in 21-day-old rats and increases in 28-day-old animals. There were few significant differences in enzyme activities in adult rats receiving pentagastrin as compared to saline.
Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP
Authors: Pandol S. J. , Dharmsathaphorn K. , Schoeffield M. S. , Vale W. , Rivier J.
Published: December 2017

From structure-activity relationship studies of rat growth hormone-releasing factor (rGFR) on the vasoactive intestinal peptide (VIP) receptor in an in vitro preparation of exocrine pancreas, we predicted that [4Cl-D-Phe6, Leu17]VIP would be a competitive antagonist for the action of VIP. Micromolar concentrations of synthetic [4Cl-D-Phe6, Leu17]VIP competitively antagonized VIP-stimulated amylase release in the pancreatic preparation and VIP-stimulated short-circuit current changes in a colonic tumor cell line. In addition, [4Cl-D-Phe6, Leu17]VIP inhibited amylase release stimulated by rGRF, high concentrations of secretin (agents that act through the VIP receptor), and peptide contaminants in a preparation of natural glucagon. Finally, [4Cl-D-Phe6, Leu17]VIP did not inhibit the action of agonists for the secretin, GRF, or glucagon receptors.
An analysis of intestinal calcium transport across the rat intestine
Authors: Bronner F. , Pansu D. , Stein W. D.
Published: December 2017

Kinetic analysis of transmural calcium transport, as evaluated by in situ intestinal loops, has confirmed the existence of two transport processes, a saturable, transcellular one that is regulated by vitamin D and predominates in the proximal intestine and a nonsaturable process similar in intensity throughout the intestine. Transport data obtained from everted sac experiments are kinetically consistent with events in the in situ loop. Analysis of the three component steps making up the saturable process, i.e., entry across the brush-border membrane, intracellular diffusion, and extrusion across the basolateral membrane, indicates that intracellular diffusion is likely to be the limiting step. Active calcium transport varies directly and proportionately with the content of calcium-binding protein (CaBP), a specific molecular expression of the action of vitamin D. Since CaBP is a cytosolic protein, it may act to facilitate calcium diffusion, a proposition advanced by Kretsinger, Mann, and Simmons and supported here quantitatively. We calculate that the rate of intracellular calcium diffusion in the absence of CaBP is only approximately 1/70 of what is found in the vitamin D-replete cell. Similar considerations have led to the proposal that calcium moved by the nonsaturable process travels largely via the paracellular route. The kinetic parameters derived here, i.e., Vm = 22 mumol X h-1 X g (wt wt-1, Km = 3.9 mM, and a nonsaturable rate of 0.16/h, can be used to predict calcium absorption data as determined in previously published balance experiments.
Potency of natural and synthetic canine gastrin-releasing decapeptide on canine antral muscle
Authors: Mayer E. A. , Reeve J. R. , Khawaja S. , Chew P. , Elashoff J. , Clark B. , Walsh J. H.
Published: December 2017

The carboxyl terminal decapeptide of gastrin-releasing peptide (GRP-10), a small, naturally occurring bombesin-like peptide, has been isolated from canine antral muscle, synthesized, and its bioactivity compared with other synthetic and natural gastrin-releasing peptides on stimulation of spontaneously occurring contractions of canine circular antral muscle in vitro. Concentrations of peptides were verified by amino acid analysis and radioimmunoassay. In this system three forms of natural canine GRP, synthetic GRP-10, synthetic porcine gastrin-releasing heptacosapeptide (GRP-27), [Gln3]GRP-10, and [Arg3]GRP-10 all were similar in potency to synthetic amphibian bombesin. These results differ from the low activity of GRP-10 previously reported in rat brain. The full biological potency on canine antral motility and the presence of GRP-10 in nerve fibers in the gut and in the spinal cord suggest a possible role for this peptide as a neurotransmitter or neuromodulator in regulation of smooth muscle contraction.
Maturation of cholecystokinin receptors in pancreatic acini of rats
Authors: Leung Y. K. , Lee P. C. , Lebenthal E.
Published: December 2017

Amylase secretion by fetal and newborn rat pancreata was shown not to respond to cholecystokinin (CCK) stimulation. Binding of 125I-Bolton-Hunter (125I-BH)-CCK-8 to dispersed pancreatic acini from rats at various perinatal ages was measured and compared with adults. Binding occurred maximally at 30 min at 37 degrees C at all ages. Maximal binding increased with age. The capacity and affinity of the CCK-receptor binding system was analyzed by Scatchard's method. The results revealed that the capacity of the high-affinity component gradually increases with age, whereas that of the low-affinity component remains relatively constant. Amylase secretion due to CCK stimulation also increases with age, suggesting that the lack of responsiveness of pancreata of pups to secretagogue is due to a low binding capacity of the high-affinity component of the receptors.
Prostaglandin interaction with histamine release and parietal cell activity in isolated gastric glands
Authors: Nylander O. , Berglindh T. , Obrink K. J.
Published: December 2017

The effects of different prostanoids on parietal cell activity and glandular histamine (Hi) release were examined in isolated rabbit gastric glands. [14C]aminopyrine accumulation and glandular oxygen consumption were used as indices of parietal cell activity, and Hi was determined fluorophotometrically in the supernatant of the glandular suspensions. Both prostaglandins (PG) E2 and E1 dose dependently (10(-8) and 10(-6) M) increased the release of endogenous Hi. Carbacyclin was less effective and PGF2 alpha was almost without effect. Hi release induced by acetylcholine (Ach) and pentagastrin (Pg) was markedly potentiated in the presence of PGE2 (10(-8) to 10(-5) M). The Ach-induced sti ulation of Hi release was also potentiated by arachidonic acid (10(-5) M), an effect that was inhibitable by the cyclooxygenase inhibitor meclofenamate (3 X 10(-5) M). Somatostatin partially inhibited the response to Pg (3 X 10(-9) M) in combination with PGE2 (10(-5) M). Atropine (10(-5) M) strongly reduced the response elicited by Ach (3 X 10(-6) M) combined with PGE2 (10(-6) M). All prostanoids inhibited Hi (10(-4) M)-induced parietal cell activity in a dose-dependent manner (60-70%) but displayed different potency. The stimulatory response to Ach (3 X 10(-6) M) or Pg (3 X 10(-9) M) in combination with isobutylmethylxanthine (IBMX, 10(-5) M) was inhibited by PGE2 in a dose-dependent fashion. PGE2 (10(-6) M) was considerably more effective than cimetidine (10(-5) M) in inhibiting IBMX (10(-4) M)-stimulated oxygen consumption, and the remaining IBMX-PGE2 response (approximately 40%) was dose dependently (10(-8) to 10(-5) M) inhibited by cimetidine. Addition of Hi (10(-7) to 4 X 10(-7) M) or Pg (3 X 10(-10) to 3 X 10(-9) M) counteracted the PGE2 inhibition of the IBMX response. In addition, IBMX (10(-4) M) combined with PGE2 (10(-6) M) gave rise to a threefold increase in Hi release. These results suggest that prostaglandins have two opposing effects, i.e., liberation of endogenous Hi and inhibition of the action of Hi on the parietal cell.
Ileal and colonic propulsive behavior: contribution of enteric neural circuits
Authors: Weems W. A. , Weisbrodt N. W.
Published: December 2017

Experiments were conducted in vitro to determine the extent to which the intrinsic propulsive behavior of cat terminal ileum and colon is controlled by the enteric nervous system (ENS) and the myogenic control system. Oral and aboral ends of terminal ileal and colonic segments, 17 cm in length, were connected to a propulsion evaluation system that imposed input-output conditions of constant capacitance and negligible resistance. To determine the effect of inhibiting one or more components within the ENS on spontaneously occurring patterns of propulsive behavior, segments were arterially perfused with tetrodotoxin (3.1 X 10(-7) M), atropine sulfate (10(-6) M), tubocurarine chloride (1.5 X 10(-6) M), hexamethonium chloride (2.8 X 10(-5) M), or methysergide (2.8 X 10(-5) M). Results indicated that when cat ileal and colonic segments are evaluated under conditions requiring significant amounts of hydrostatic work to effect fluid ejection 1) the unmodulated myogenic control system is unable to induce significant amounts of fluid expulsion, 2) cholinergic excitatory motor neurons of the ENS are required for the generation of the intrinsic patterns of propulsive behavior normally observed to expel fluid, and 3) the spontaneous occurrence of intrinsic propulsive patterns requires the operation of ENS integrative mechanisms utilizing nicotinic cholinergic and serotonergic synapses.
Contrasting cholinergic dependence of pancreatic and gallbladder responses to cholecystokinin
Authors: Strah K. M. , Pappas T. N. , Melendez R. L. , Debas H. T.
Published: December 2017

Cholinergic receptors for cholecystokinin (CCK) have been identified on neurons of the enteric nervous system, including those of the gallbladder. To determine whether any differences exist in the extent to which CCK action depends on muscarinic cholinergic receptors in the pancreas and gallbladder, 11 dogs with pancreatic and 7 dogs with biliary fistulas were given increasing doses of intravenous CCK-8 (15-250 ng X kg-1 X h-1) or intraduodenal sodium oleate (0.1-9 mmol/h) with and without atropine pretreatment. Pancreatic protein response to CCK-8 was dose dependent, reaching a maximal of 448 +/- 76 mg/15 min at the highest dose. Atropine pretreatment caused nonsignificant reduction in the response to the lowest dose but had no effect on the responses to the other doses, with the response to the highest dose of CCK being 473 +/- 82 mg/15 min. In contrast, gallbladder contraction as measured by bile fistula bilirubin output was very sensitive to inhibition by atropine. Bilirubin responses to 16, 32, 62.5, 125, and 250 ng X kg-1 X h-1 were 14 +/- 5, 18 +/- 5, 28 +/- 5, 36 +/- 6, and 52 +/- 12 mg/h, respectively, without atropine and 0 +/- 0, 6 +/- 2, 7 +/- 2, 18 +/- 4, and 18 +/- 4 mg/h with atropine pretreatment. Similarly, pancreatic responses to sodium oleate infusion were less susceptible to inhibition by atropine than were the gallbladder responses. With respect to pancreatic protein secretion, the response to only the lowest dose of sodium oleate was significantly inhibited by atropine.(ABSTRACT TRUNCATED AT 250 WORDS)
Specific binding and degradation of somatostatin by membrane vesicles from pig gut
Authors: Weber M. , Cole T. , Conlon J. M.
Published: December 2017

Plasma membrane vesicles were prepared from the basolateral face of pig small intestinal epithelial cells and were enriched in the activity of Na+-K+-ATPase (9-fold relative to the cell homogenate) and ranged in size from 0.15 to 0.40 micron diam. Incubation of somatostatin-14 and [125I-Tyr11]-somatostatin-14 with the vesicles at 37 degrees C resulted in rapid proteolytic degradation of the peptides. Metabolites were isolated by reverse-phase high-performance liquid chromatography and identified by amino acid composition. Cleavages between Ala1-Gly2, Phe6-Phe7, Phe7-Trp8, and Thr10-Phe11 were observed, indicative of aminopeptidase and endopeptidase action. Degradation was inhibited by 1,10-phenanthroline and by bacitracin, and in the presence of these inhibitors and at 21 degrees C binding of [125I-Tyr11]somatostatin-14 to the vesicles was observed. Binding was inhibited in a concentration-dependent manner by somatostatin-14 (half-maximal inhibition at 2.0 +/- 0.1 nM) and by somatostatin-28 (0.8 +/- 0.1 nM) but not by structurally unrelated peptides. The rate of degradation of [125I-Leu8, D-Trp22, Tyr25]somatostatin-28 by basolateral membrane was less than 20 fold that of [125I-Tyr11]somatostatin-14 and a two- to three-fold enhanced binding to the vesicles was observed. Analysis of the inhibition of binding of this analogue by somatostatin-28 indicates the presence of single class of binding site with Kd = 1.3 +/- 0.3 nM. Rapid degradation but no specific binding of somatostatin-14 by brush-border membranes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of refeeding on polyamine biosynthesis in isolated enterocytes
Authors: Fitzpatrick L. R. , Wang P. , Eikenburg B. E. , Haddox M. K. , Johnson L. R.
Published: December 2017

Ornithine decarboxylase (ODC) activity has been found to be preferentially associated with small intestinal villus cells rather than crypt cells in the rat. In the present study, ODC, S-adenosylmethionine decarboxylase (SAMDC), and polyamines were measured in isolated enterocytes to determine which cell populations increased polyamine biosynthetic activity after refeeding. Two hours following refeeding, significant increases in ODC were observed in villus tip (10 times) and midvillus (20 times) enterocytes. No increase in ODC activity was found in isolated crypt cells. A similar pattern was observed for SAMDC. Enzyme activity increased in villus tip (2 times) and midvillus (27 times) cells but not in crypt enterocytes. Putrescine contents were increased following refeeding in midvillus enterocytes (P less than 0.05) and in crypt cells (P less than 0.05). The accumulation of putrescine in midvillus cells occurs via ODC-induced biosynthesis, whereas in crypt enterocytes it may be due to putrescine uptake. The lack of induction of ODC and SAMDC in crypt enterocytes following acute refeeding suggests these enzymes are apparently not involved in the initiation of cell proliferation known to occur under this condition.