bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative effects of systemic pH, PCO2, and HCO3 concentration on colonic ion transport
Authors: Charney A. N. , Haskell L. P.
Published: December 2017

To determine the relative effects of systemic pH, PCO2, and bicarbonate concentration on colonic electrolyte transport, states of acute metabolic acidosis and alkalosis were created in Sprague-Dawley rats by gavage feeding (NH4)2SO4 and NaHCO3, respectively. During in situ perfusion of the distal colon in pentobarbital-anesthetized animals, electrolyte transport was measured before and after respiratory compensation of the systemic pH. Acute respiratory acidosis and alkalosis also were studied by ventilating animals with 0, 3, or 8% CO2. When animals in all groups were considered, net sodium absorption correlated well with blood PCO2 (r = 0.99) but not with blood pH. Net bicarbonate secretion correlated with the plasma (r = 0.95) and luminal (r = -0.63) bicarbonate concentrations but not with blood pH or PCO2. Net chloride absorption correlated with both blood PCO2 (r = 0.92) and the plasma bicarbonate concentration (r = 0.80). These results suggest that systemic PCO2 affects a sodium chloride absorptive process and that the plasma bicarbonate concentration affects a chloride absorptive-bicarbonate secretory exchange process in the rat colon.
Effects of nicotine on canine intestinal blood flow and oxygen consumption
Authors: Gallavan R. H. , Tsuchiya Y. , Jacobson E. D.
Published: December 2017

The purpose of this study was to determine the effects of nicotine on intestinal blood flow and oxygen consumption. The intravenous infusion of nicotine at doses corresponding to those experienced by smokers produced a transient increase in systemic arterial blood pressure and mesenteric blood flow. Subsequently a steady-state response developed that consisted of a reduction in mesenteric blood flow due to both a decrease in blood pressure and an increase in intestinal vascular resistance. This increase in resistance was probably due to increased levels of circulating catecholamines. The intra-arterial infusion of nicotine into the intestinal circulation at doses experienced by the average smoker had no effect on either intestinal blood flow or oxygen consumption. Similarly, under in vitro conditions nicotine had no direct effect on intestinal vascular smooth muscle tension. Thus, nicotine appears to reduce intestinal blood flow indirectly as a result of its systemic effects.
A human colonic tumor cell line that maintains vectorial electrolyte transport
Authors: Dharmsathaphorn K. , McRoberts J. A. , Mandel K. G. , Tisdale L. D. , Masui H.
Published: December 2017

A human colonic epithelial cell line, T84, derived from a colonic carcinoma, has been examined both morphologically and functionally. The cells grew to confluence as a monolayer with the basolateral membrane attached to the surface of the culture dish and a microvillus-studded apical membrane facing the media. Tight junctions and desmosomes were demonstrated between adjacent cells. Confluent monolayer cultures conducted vectorial electrolyte transport that could be altered by a variety of secretagogues and antisecretagogues similar to isolated intestinal tissues. This cell line will serve as an excellent model system for the study of electrolyte transport processes and their regulation by peptide hormones and neurotransmitters.
Effects of stimulation of nucleus ambiguus complex on gastroduodenal function
Authors: Pagani F. D. , Norman W. P. , Kasbekar D. K. , Gillis R. A.
Published: December 2017

We investigated the effects of stimulation of the nucleus ambiguus (NA) complex on gastroduodenal motility and gastric secretion in alpha-chloralose-anesthetized cats. Motility was measured by use of extraluminal force transducers sutured to the body, antrum, pylorus, and duodenum. Secretion was measured by determining changes in gastric pH, titratable acidity, and pepsinogen activity. Stimulation of the NA complex (right NA in 11 animals and left NA in 8 animals) elicited contractions of the antrum, pylorus, and duodenum, as well as sinus bradycardia and hypotension using stimulus parameters of 133 microA, 50 Hz, and 0.2-ms pulse duration. Both the motility and cardiovascular responses evoked by electrical stimulation of the NA complex were prevented by ipsilateral vagotomy. The optimum stimulus frequency for eliciting increases in gastroduodenal motility was 50 Hz. Frequencies higher than 50 Hz resulted in attenuated motility responses. This was not true of the heart rate response, as sinus bradycardia was maximal at 10 Hz and was maintained to 100 Hz. Electrical stimulation of the NA complex (8 animals) had no effect on pepsinogen secretion or titratable acidity, but produced a small (0.21 pH units) but significant increase in gastric pH. These results indicate that 1) stimulation of the NA complex results in pronounced increases in motility mediated by the ipsilateral vagus nerve, and 2) the pathways mediating these motility responses appear to involve more synapses than the pathways mediating the motor responses to the heart.
Intravenous mixed amino acids and fats do not stimulate exocrine pancreatic secretion
Authors: Stabile B. E. , Borzatta M. , Stubbs R. S. , Debas H. T.
Published: December 2017

We compared the responses of the canine exocrine pancreas to intraduodenal versus intravenous administration of mixed amino acids, fat emulsion, and glucose. Graded doses of amino acid mixture and of fat emulsion gave graded responses in volume, protein, and bicarbonate when administered intraduodenally. In contrast, the same doses of the amino acid mixture and fat emulsion administered by central intravenous infusion caused no significant pancreatic secretion of volume, protein, or bicarbonate. Graded doses of glucose caused no statistically significant pancreatic secretion whether they were given intraduodenally or intravenously. We conclude, contrary to a previously published observation, that amino acids and fats given parenterally do not stimulate pancreatic secretion. As a corollary, it is reasonable to assume that the pancreas is not stimulated during total parenteral nutrition with acute pancreatitis or a pancreatic fistula.
Neuromuscular structures in opossum esophagus: role of interstitial cells of Cajal
Authors: Daniel E. E. , Posey-Daniel V.
Published: December 2017

The structures of the lower esophageal sphincter (LES) and body circular muscle (BCM) from opossum were compared as to neural and muscular structures and the structural relations of interstitial cells of Cajal to nerves and muscle cells. Both LES and BCM were densely innervated by nerves with varicosities containing many small agranular vesicles and a few large granular vesicles. These nerves were more closely related structurally to the interstitial cells of Cajal than to smooth muscle cells. More gap junctions were observed between smooth muscle cells and between interstitial cells of Cajal and smooth muscle cells in BCM than in LES. Those between smooth muscle cells were larger in BCM. Complete relaxation of the LES strip by isoproterenol reduced these differences but did not eliminate them. The finding that interstitial cells of Cajal often had gap-junction contacts to smooth muscle and close associations with nerves is consistent with the hypothesis that interstitial cells are intercalated between the nerves and muscles and may mediate nerve responses. These findings also suggest that LES muscle cells may be less well coupled electrically than BCM muscle cells.
Splanchnic arterial blood flow in rats with portacaval shunts
Authors: More N. , Lobosotomayor G. , Basse-Cathalinat B. , Bedin C. , Balabaud C.
Published: December 2017

With indirect methods, it was shown in rats with portacaval shunts (PCS) that total hepatic blood flow (THBF) remained constant when expressed per gram of liver. These results implied an absolute increase in hepatic arterial blood flow (HABF). The aim of this study was to investigate HABF and splanchnic nonhepatic arterial blood flow (SNHABF) with a direct method (57Co microspheres) in PCS rats. One month after surgery, the following results were obtained in PCS rats compared with pair-fed, sham-operated rats: 1) liver mass atrophy was 42.3 +/- 10.9%, 2) HABF (ml X min-1 X g liver-1) was increased by a factor of 2.7, 3) SNHABF (ml X min-1 X 100 g body wt-1) was higher (9.8 +/- 3.3 vs. 5.6 +/- 2.7) (P less than 0.05) and 4) THBF (ml X min-1 X g liver-1) was decreased (1.36 +/- 0.34 vs. 1.85 +/- 0.86) but not significantly. Increases in HABF and SNHABF were not the direct consequence of an increase in cardiac output as attested by a normal cerebral blood flow (ml X min-1 X g organ-1) in PCS rats. In PCS rats, an increase in HABF may prevent the further spread of liver necrosis. The cause and the reason for an increase in SNHABF remain unknown.
A lower esophageal sphincter reflex involving substance P
Authors: Reynolds J. C. , Ouyang A. , Cohen S.
Published: December 2017

The purpose of this study was to determine the mechanism by which distal esophageal acidification increases lower esophageal sphincter (LES) pressure in the anesthetized cat. Intraluminal pressures and myoelectric activity were recorded using fixed, localized manometric catheters and serosal bipolar silver-silver chloride electrodes. The increase in LES pressure (27.1 +/- 4.9 mmHg) and spike activity (133.8 +/- 22.6 spikes/min) following distal esophageal acidification were greater than after saline (P less than 0.001). These responses were abolished by either tetrodotoxin (intravenously) or intraluminal ethyl aminobenzoate. The responses were not antagonized by bilateral cervical vagotomy or by atropine, hexamethonium, phentolamine, propranolol, diphenhydramine, cimetidine, cinanserin, naloxone, haloperidol, or proglumide. Tachyphylaxis to substance P abolished the LES pressure and spike responses to exogenous substance P and to distal esophageal acidification but had no effect on the LES responses to phenylephrine (25.0 micrograms/kg iv) or pentagastrin (0.5 microgram/kg iv). The putative substance P antagonist [D-Pro2,D-Trp7,9]substance P was a partial antagonist and a weak agonist on the LES. Large doses of [D-Pro2,D-TRP7,9]substance P (200.0 micrograms/kg iv) gave a 61.3 +/- 19.3% inhibition of the LES pressure response to acid (P less than 0.05). Intravenous tetrodotoxin partially antagonized the LES response to substance P (10.0 micrograms/kg iv). These studies suggest that the increases in LES pressure and spike activity following distal esophageal acidification occur through a spike-associated enteric neural reflex that involves substance P as a neurotransmitter.
Colonic migrating and nonmigrating motor complexes in dogs
Authors: Sarna S. K. , Condon R. , Cowles V.
Published: December 2017

We report here the characteristics of a cyclic motor activity in the colon of conscious dogs and its relationship to small intestinal migrating motor complexes (MMCs). The colonic motor activity was recorded by four equispaced strain gauges and small intestinal myoelectric activity by four equispaced bipolar electrodes. The colonic motor activity was characterized by rhythmic bursts of contractions. The mean durations of bursts of contractions varied from 7.0 to 11.5 min at the four colonic recording sites. Those bursts of contractions which migrated over at least three recording sites were called colonic migrating motor complexes (CMMCs). All other patterns of bursts of contractions were called colonic nonmigrating motor complexes (CNMCs). A total of 160 CMMCs were recorded during a total recording period of 132 h; 151 CMMCs migrated caudad and 9 orad. The mean period of caudad migrating CMMCs was 53.3 +/- 5.4 (SE) min, and their mean migration time was 11.3 +/- 1.2 (SE) min. The onset of CMMCs was not temporally related to the onset of small intestinal migrating myoelectric complexes in the duodenum or their arrival in the terminal ileum. CMMCs did not have phases I to IV like those of small intestinal MMCs, but two consecutive CMMCs were separated by a quiescent state or by one or more randomly occurring bursts of contractions (CNMCs).
Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle
Authors: Sanders K. M.
Published: December 2017

Studies were performed to determine the role of endogenous prostaglandins (PG) in regulating mechanical and electrical activities of canine ileal circular muscles. Indomethacin, a prostaglandin synthesis blocker, enhanced the amplitude of spontaneous and acetylcholine-stimulated contractions. The increase in mechanical activity caused by indomethacin was accompanied by decreased release of 6-keto-PGF1 alpha, the spontaneous metabolite of prostacyclin, from the muscle. The electrical mechanisms responsible for the changes in mechanical activity caused by indomethacin were investigated by intracellular measurement of electrical activity. The enhanced contractions due to indomethacin correlated with enhanced electrical slow-wave amplitude and generation of action potentials. After indomethacin treatment muscles were exposed to several exogenous prostaglandins to determine which of these compounds might reverse the mechanical effects of indomethacin. Prostacyclin reversed the effects of indomethacin, and PGE2 reversed some of the effects of indomethacin. Prostacyclin also decreased the amplitude of electrical slow waves and abolished action potentials. These electrical effects were associated with decreased contractile amplitude. It is concluded that the dominant prostaglandin responsible for the "prostaglandin effect" in canine ileal circular muscle must be inhibitory to spontaneous and acetylcholine-stimulated contractions. The mechanical effects attributed to endogenous prostaglandin appear to be due to an electrical mechanism. Based on the evidence presented prostacyclin emerges as the most likely candidate for the role of "dominant" prostaglandin, but PGE2 may also contribute as a modulator of electrical and mechanical activities.
Effect of dietary fibers on rat large bowel mucosal growth and cell proliferation
Authors: Jacobs L. R. , Lupton J. R.
Published: December 2017

The effects of three different fibers on large intestinal mucosal mass per unit length, crypt morphometrics, and cytokinetics were compared by feeding fiber supplements to 40 rats for 4 wk. A control group of rats was fed a fiber-free diet and the experimental groups received the same diet, uniformly diluted by the addition (wt/wt) of 20% oat bran, 10% pectin, or 10% guar. All groups of rats exhibited equal caloric intakes and weight gains. Guar consistently produced an increase in cecal and colonic mucosal wet weight, DNA, and RNA when compared with the control group (P less than 0.05). DNA levels were increased in the cecum and proximal colon of the pectin group but remained unaltered in those rats fed oat bran. Autoradiographic measurements demonstrated that epithelial cell turnover time was longer in the distal colon of the guar and pectin groups (P less than 0.001), but shorter in the proximal colon of the oat bran group, when compared with the controls (P less than 0.01). This comparative study provides further insight into the possible mechanisms by which specific dietary fibers elicit a hyperproliferative response in the large bowel.
Role of enkephalins in regulation of basal intestinal water and ion absorption in the rat
Authors: Fogel R. , Kaplan R. B.
Published: December 2017

Intraluminal administration of naloxone (10(-4) M), a mu-opiate receptor antagonist, or diprenorphine (10(-6) M), an opiate receptor antagonist with high affinity for both delta- and mu-receptors, decreased basal in vivo water and electrolyte absorption in the jejunum and ileum but not the colon of the rat. Diprenorphine (10(-5) M) decreased basal colonic water transport. These changes were not due to a reduction in mucosal Na-K-ATPase activity. Intravenous atropine prevented as well as abolished the changes in water transport due to naloxone. The diprenorphine-induced changes were not altered by atropine. Naloxone and diprenorphine acted by different receptors. Pretreatment with naloxone (10(-4) M) prevented the increase in water transport due to morphine, a mu-agonist, whereas a higher concentration of naloxone (10(-3) M) was required to inhibit the increase due to D-Ala-methionine-enkephalinamide, a delta-receptor agonist. In contrast, diprenorphine (10(-6) M) abolished the absorption caused by morphine and D-Ala-methionine-enkephalinamide. Diprenorphine (3 X 10(-7) M) partially prevented the morphine-induced increase in water absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolation of stable pancreatic zymogen granules
Authors: De Lisle R. C. , Schulz I. , Tyrakowski T. , Haase W. , Hopfer U.
Published: December 2017

Isolated pancreatic zymogen granules have been reported to lyse in common electrolyte solutions such as NaCl or KCl or at pH values above 5.5. A new method, based on an isosmotic Percoll density gradient, was developed for the isolation of zymogen granules and applied to rat pancreas. The granules are highly purified as judged by electron microscopic appearance and specific amylase activity. These granules exhibit a high degree of stability at physiological pH and in isotonic NaCl or KCl. Zymogen granule diameters, determined with a Coulter Counter, were 1.0 +/- 0.2 micron in either isotonic NaCl and KCl. These size values, obtained in physiological solutions, are comparable with granule sizes determined in intact cells by microscopy. Amylase activity averaged 0.66 microU per granule and protein content averaged 0.31 pg per granule; these values were not significantly influenced by different conditions of pH between 5.5 and 7.0 and ionic strength from near 0 to 0.15. The granule density estimated from the protein content was 1.13 g/ml, which agrees well with the behavior of granules in a density gradient. The properties of zymogen granules from the new preparation rectify the apparent discrepancy between their role as a storage organelle and their previously reported in vitro instability.
Amylase secretion by isolated pancreatic acini after acute cholecystokinin treatment in vivo
Authors: Otsuki M. , Okabayashi Y. , Ohki A. , Hootman S. R. , Baba S. , Williams J. A.
Published: December 2017

A single dose of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier was injected subcutaneously into rats 2 and 14 h before the removal of the pancreas and the preparation of isolated pancreatic acini. CCK8 treatment induced no significant change in body weight or total amount of pancreatic DNA, but pancreatic weight, total pancreatic protein and amylase, and the concentration of amylase and total protein relative to DNA were significantly decreased. In acini prepared from CCK8-pretreated rats, responsiveness to maximal and supramaximal concentrations of CCK8 was significantly increased, irrespective of whether the amount of amylase released was expressed relative to DNA or calculated as a percentage of the acinar content. The dose-response curves for CCK8 were similarly shaped in both CCK8-pretreated and control rats but shifted threefold toward higher concentrations of CCK8 2 or 14 h after CCK8 treatment. Specific 125I-CCK binding was significantly increased only for high-affinity binding sites. Although these observations suggest that alterations in pancreatic amylase release could be due to changes at the cholecystokinin receptor, the secretory responsiveness to maximal and supramaximal concentrations of carbachol was also increased without any change in the sensitivity. Moreover, in contrast to the cholecystokinin receptor, there was no change in the number of muscarinic receptors or in their affinity for either agonists or antagonists measured with [3H]quinuclidinyl benzilate.(ABSTRACT TRUNCATED AT 250 WORDS)
Microelectrode measurements of K+ and pH in rabbit gastric glands: effect of histamine
Authors: Kafoglis K. , Hersey S. J. , White J. F.
Published: December 2017

Conventional and liquid ion-exchange microelectrodes sensitive to K+ or pH were used to examine the response of isolated rabbit gastric glands to histamine. The epithelial cells were impaled across the basolateral membrane. The membrane potential averaged -6.1 +/- 0.6 mV and was unchanged after replacement of medium K+, Cl-, or Na+. The intracellular K+ activity (alpha iK) averaged 41.3 +/- 3.0 mM, indicating K+ accumulation by a factor of 6.8. Active accumulation of K+ was eliminated by ouabain. In contrast, histamine increased K+ activity to 55.3 +/- 3.9 mM. This stimulation was blocked by ouabain. In glands bathed in a Na+-free medium containing ouabain, addition of histamine elevated alpha iK from 12.5 +/- 0.7 to 17.1 +/- 1.1 mM. Isobutylmethylxanthine (10(-4) M) also elevated alpha iK. When impaled with pH-sensitive microelectrodes, glands exposed to histamine exhibited regions of acidity as low as pH 3. Acidification was also produced by histamine after medium Na+ had been replaced with choline. Picoprazole (H 149/94) blocked the effects of histamine on alpha iK and gland pH. The results are consistent with the view that histamine-induced acid secretion by gastric glands is associated with K+ uptake by a mechanism that is independent of Na+ transport but is inhibited by intracellular Na+. This is most likely the H+-K+-ATPase on the secretory surface of the gland cells. Evidence that some tissue K+ is bound or compartmentalized is also discussed.
Regulation of digestion. II. Effects of insulin and glucagon on pancreatic secretion
Authors: Tseng H. C. , Grendell J. H. , Rothman S. S.
Published: December 2017

The endocrine islet-cell hormones insulin and glucagon are secreted at high concentrations into an intrapancreatic portal circulation and have been reported to affect the secretion of digestive enzyme by the exocrine pancreas. In the present experiments, insulin and glucagon were injected into the celiac artery of anesthetized rats to evaluate their effects on the secretion of amylase and trypsinogen by the pancreas. Neither hormone when given alone significantly changed the output of either enzyme. However, when given with the pancreatic secretagogue cholecystokinin, each altered the effect of injection of cholecystokinin. In a dose-dependent fashion insulin increased trypsinogen output without affecting amylase output, whereas glucagon inhibited amylase output and left trypsinogen output unchanged. Thus, both hormones produced a more trypsinogen-dominant pancreatic juice than that observed with cholecystokinin alone, although in different ways. These findings suggest that the endocrine hormones insulin and glucagon may regulate secretion of digestive enzymes by the pancreas by modulating the response to stimuli of overall protein secretion such as cholecystokinin.
Specificity of an Na+ -dependent taurocholate transport site in isolated rat hepatocytes
Authors: Hardison W. G. , Bellentani S. , Heasley V. , Shellhamer D.
Published: December 2017

The structural specificity of the taurocholate uptake mechanism was studied by determining the ability of 100 microM structural analogues of taurocholate to inhibit the uptake of 5 microM [14C]-taurocholate into freshly isolated rat hepatocytes. Taurocholate was a more potent inhibitor than cholate. The fewer the number of hydroxyl groups, the more potent the inhibitors. Neither hydroxyl group orientation (alpha or beta) nor esterification with formic acid strongly influenced inhibitory potency. Replacement of hydroxyl groups with keto groups, however, diminished inhibitory potency. These facts suggested that distortion of the sterol backbone may be an important factor in diminishing inhibitory potency. Charge on the nonsteroid moiety affected potency. Both neutral and negatively charged compounds inhibited more strongly than positively charged compounds. As important as charge, however, was length of the nonsteroidal moiety. Inhibitory potency increased progressively as length beyond C-17 increased up to 11 A. Inhibitory potency was reduced again, however, with an extremely long end group of 18 A. The inhibitors do not act as cytotoxins since cellular oxygen consumption was not diminished by any of them. Furthermore, inhibition was specific for the taurocholate uptake mechanism. The three most potent inhibitory compounds inhibited L-alanine uptake little or not at all. The kinetics of inhibition, determined for three selected compounds, were consistent with competitive inhibition. The structural specificity of the rat hepatocyte sodium-dependent taurocholate uptake site is similar to that of the guinea pig ileum uptake site.
Release of 86Rb from rat submandibular gland slices: relation to sodium pump activity
Authors: Stewart D. J. , Laansoo M. , Sen A. K.
Published: December 2017

Slices of rat submandibular gland were preloaded with 86Rb, an isotope that can substitute for K+ in the K+ release process. The efflux of 86Rb was monitored in a superfusion apparatus that efficiently removed the 86Rb as it exited from the tissue slices. Carbachol and the calcium ionophore A23187 activated a calcium-dependent increase in 86Rb efflux. Dibutyryl cGMP had no detectable effect on 86Rb efflux in contrast to its activation of ouabain-sensitive uptake of 86Rb observed in an earlier study. The stimulated release of 86Rb was not dependent on the presence of either sodium or chloride ions. When 86Rb efflux was stimulated by carbachol, the efflux rate returned toward the basal rate after a few minutes of exposure to carbachol in the medium. If ouabain was then introduced into the superfusate, a large increase in efflux was stimulated. In the absence of carbachol, only a small increase in 86Rb efflux was stimulated by ouabain. The effect of ouabain indicates that there was a substantial recycling of 86Rb between the release and uptake processes in the extracellular space of the tissue slice. The significance of this observation is discussed.
Effect of intraluminal pH on cholesterol and oleic acid absorption from micellar solutions in the rat
Authors: Chijiiwa K. , Linscheer W. G.
Published: December 2017

We have studied the effects of intraluminal pH on micellar solubilization and on absorption rate of oleic acid (OA) and cholesterol in proximal small bowel segments and the total small bowel in rats. In addition, pH effect on fecal excretion of [3H]cholesterol was studied over a period of 4 days after duodenal administration of cholesterol in solutions at different pH using beta-sitosterol as a nonabsorbable marker. Rates of absorption of OA and cholesterol were, respectively, 1.8 and 1.9 times higher at pH 5.5 in both proximal bowel segments as compared with pH 6.5 (P less than 0.001). Similar observations were made when the whole small bowel was perfused. At pH 5.5, 1.8 times more OA was absorbed and 1.5 times more cholesterol than at pH 6.5 (P less than 0.001). Also, fecal output of radioisotope following administration of pH 5.5 solution was only 47% of the excretion using the pH 6.5 solution. Excretion of beta-sitosterol, which serves as a nonabsorbable marker, was not affected by pH differences. In vitro measurements of micellar solubility at the two pH levels by ultracentrifugation showed that an increase of one pH unit resulted in a decreased number of particles in the oil phase (oleic acid and cholesterol in the emulsified particles in pH 6.5 solution is 37 and 34%, respectively, of that in the pH 5.5 solution) due to increased solubilization into the micellar phase. Measurements of monomer activities of OA and cholesterol using a polyethylene disk technique showed a significantly higher activity at the lower pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Somatostatin modulation of peptide-induced acetylcholine release in guinea pig ileum
Authors: Teitelbaum D. H. , O'Dorisio T. M. , Perkins W. E. , Gaginella T. S.
Published: December 2017

The peptides caerulein, neurotensin, somatostatin, and substance P modulate the activity of intestinal neurons and alter gut motility. We examined the effects of these peptides on acetylcholine release from the myenteric plexus and intestinal contractility in vitro. Caerulein (1 X 10(-9) M), neurotensin (1.5 X 10(-6) M), and substance P (1 X 10(-7) M) significantly enhanced the release of [3H]acetylcholine from the myenteric plexus of the guinea pig ileum. This effect was inhibited by tetrodotoxin (1.6 X 10(-6) M). Somatostatin (10(-6) M) inhibited caerulein- and neurotensin-evoked release of acetylcholine but did not inhibit release induced by substance P. Caerulein, neurotensin, and substance P caused contraction of the guinea pig ileal longitudinal muscle. Somatostatin inhibited the contractions induced by caerulein and neurotensin. In contrast, substance P-induced contraction was not inhibited significantly by somatostatin. Thus, in the guinea pig ileum, caerulein-, neurotensin-, and substance P-induced contractility is due, at least in part, to acetylcholine release from the myenteric plexus. The ability of somatostatin to inhibit peptide-induced contractility is selective, and its mechanism may be attributed to inhibition of acetylcholine release.
Arachidonic acid and postprandial intestinal hyperemia
Authors: Mangino M. J. , Chou C. C.
Published: December 2017

The effects of prostaglandin synthesis on food-induced increases in intestinal blood flow and O2 uptake were examined in the jejunum of anesthetized dogs. Intravenous (40 micrograms X kg-1 X min-1) or intra-arterial (0.8-1.6 microgram X min-1) infusions and luminal placement (6.5 X 10(-4) M or 200 micrograms/ml) of arachidonic acid (AA) significantly attenuated the food-induced jejunal hyperemia. Furthermore, luminal placement of AA significantly attenuated the food-induced increase in jejunal O2 uptake. Changes in blood flow and O2 uptake were significantly correlated both before and after arachidonic acid administration. Although intravenous infusion of AA decreased blood flow, intra-arterial infusion and luminal placement of AA did not significantly alter resting blood flow under free-flow conditions. In another series of experiments, intravenous infusions of AA under constant-flow conditions produced a biphasic response: vascular resistance rose when local blood AA concentration was raised to the range between 1 and 6 micrograms/ml blood and fell when the concentration was raised between 8 and 12 micrograms/ml blood. This study indicates that prostaglandin synthesis has a marked effect on both resting intestinal blood flow and postprandial intestinal hyperemia. The attenuation of the hyperemia may be due to its attenuation of the food-induced increase in intestinal oxidative metabolism.
Plasma secretin and pancreatic response to various stimulants including a meal
Authors: Gyr K. , Beglinger C. , Fried M. , Grotzinger U. , Kayasseh L. , Stalder G. A. , Girard J.
Published: December 2017

In dogs with gastric and duodenal Thomas cannulas, we investigated the threshold dose range of exogenous secretin and intraduodenal HCl for pancreatic bicarbonate secretion and, with a recently developed radioimmunoassay, measured the increase in plasma secretin concentrations. Synthetic secretin (2.5, 7.5, and 22.5 ng X kg-1 X h-1) was dissolved in saline or 0.1% dog albumin and given with or without a background infusion of 30 ng X kg-1 X h-1 of caerulein. The minimal dose of secretin that elicited a significant pancreatic bicarbonate response as well as an increase in plasma secretin concentration was 7.5 ng X kg-1 X h-1 when administered with albumin and 22.5 ng X kg-1 X h-1 without albumin. The threshold dose for duodenal HCl was 2 mmol X h-1. The threshold secretin dose for bicarbonate secretion and for an increase in plasma secretin levels was unchanged with a background caerulein infusion. Furthermore, postprandial secretin concentrations were measured. After a meat meal plasma secretin release appeared to occur in spikes up to 10 pmol X l-1 corresponding to secretin levels seen during infusion of 7.5 ng X kg-1 X h-1 of secretin and intraduodenal acid perfusion at a dose of 2 mmol X h-1.
Effects of food intake and cholecystokinin on plasma trypsinogen levels in dogs
Authors: Reidelberger R. D. , O'Rourke M. , Durie P. R. , Geokas M. C. , Largman C.
Published: December 2017

Concentrations of plasma immunoreactive anionic and cationic trypsin(ogen) were monitored in unanesthetized dogs to investigate diurnal variation, response to food intake, and effects of cholecystokinin octapeptide (CCK-8) plus secretin administration. Identical meals were consumed at the beginning and end of a 24-h period. Plasma levels of both trypsin(ogen)s increased significantly within 30 min of feeding. Second-meal responses were much larger than those following the first meal. Plasma cationic trypsin(ogen) was also elevated during the normal feeding period when food was withheld and dogs in adjacent cages were fed. Small, irregular variations in plasma trypsin(ogen)s occurred during the interdigestive period when blood was sampled every 2 h. CCK-8 plus secretin, in doses shown previously to stimulate exocrine secretion of enzymes submaximally, increased plasma levels of both trypsin(ogen)s dose dependently. Most (greater than 80%) of the immunoreactive cationic trypsin(ogen) in plasma before and after feeding and following CCK-8 was in proenzyme form. We conclude that plasma levels of pancreatic trypsinogens are increased by food intake and low doses of CCK-8. Furthermore, cephalic mechanisms appear to play an important role in mediating the response to food intake.
Food proteins and gut mucosal barrier I. Binding and uptake of cow's milk proteins by adult rat jejunum in vitro
Authors: Stern M. , Walker W. A.
Published: December 2017

To study small intestinal binding, breakdown, and uptake of bovine serum albumin (BSA) and beta-lactoglobulin ( BLG ), radiolabeled with 125I or 14C, the rat everted gut sac technique was used as a model of intestinal protein handling. Binding and uptake were found to be nonspecific and nonsaturable. There was a close correlation between both processes (r = 0.8). A consistent difference between BSA and BLG was shown in that more BLG was bound and taken up between 1 and 30 min than was BSA (P less than 0.001). As shown by trichloroacetic acid precipitation and gel filtration on Sephadex G-100 and Bio-Gel P-2, this difference was due to differential protein breakdown that takes place during protein attachment and transport across the intestinal mucosa. High-molecular-weight fragments were generated from BSA, whereas the molecular weight of most fragments generated from BLG was very low (mol wt less than 500). Size and structure of these food protein fragments might not only influence their intestinal binding and uptake characteristics but might also play a role in the physiological induction of tolerance and their relative antigenic potential.
Adrenergic nervous control of cAMP-mediated amylase secretion in the rat pancreas
Authors: Pearson G. T. , Singh J. , Petersen O. H.
Published: December 2017

In this study of nervous control of exocrine secretion, electrical field stimulation (FS) evoked a marked, tetrodotoxin-sensitive increase in the amylase output from in vitro segments of rat pancreas. Blockade of the large cholinergic component of the response by atropine revealed a smaller noncholinergic nerve-mediated secretion. This noncholinergic secretion was unaffected by phentolamine but abolished by propranolol, as were the secretory responses to norepinephrine and other beta-adrenergic agonists. FS also produced an increase in the efflux of radiolabeled norepinephrine from preloaded tissue that was tetrodotoxin sensitive and calcium dependent. Although FS and the adrenergic secretagogues had no effect on 45Ca2+ metabolism or acinar cell electrical properties of atropine-treated rat pancreas, they both evoked increases in tissue cAMP levels. These increases in cAMP concentration were also blocked by propranolol. The phosphodiesterase inhibitor isobutylmethylxanthine potentiated both the elevation of cAMP levels and the amylase secretion evoked by adrenergic stimulation. Since both specific beta 1- and beta 2-adrenergic agonists elevated cAMP levels and caused amylase secretion, it appears that both beta-receptor subtypes are present in the rat pancreas. Of the selective beta 1- and beta 2-antagonists used, the most pronounced reduction, but not complete blockade, of the FS- and norepinephrine-induced cyclic nucleotide and secretory effects was obtained with the beta 1-antagonist metoprolol. It is concluded that stimulation of adrenergic nerves in the rat pancreas evokes an amylase secretion that is mediated via the activation of mainly beta 1-type adrenergic receptors and the utilization of cAMP as an intracellular second messenger.
Fructose-1,6-biphosphatase activity in the intestinal mucosa of developing rats
Authors: Westbury K. , Hahn P.
Published: December 2017

Fructose-biphosphatase (EC 3.1.3.11) activity was determined in the proximal and distal parts of the small intestinal mucosa of rats 1-30 days of age. Activity was found to increase to a maximum on about the 10th postnatal day and then to decrease. It was always higher in the proximal than in the distal portion of the gut. The enzyme showed a wide range of pH optimum around 7.0 and was inhibited by AMP. In 10-day-old rats activity determined 24 or 48 h after a single injection of cortisone or triiodothyronine was significantly decreased. This effect was no longer found for cortisone in 14-day-old animals. Weaning 18-day-old rats to a high-fat diet for 5 or 7 days delayed but did not prevent the usual decrease in activity seen at weaning.
Modulation of jejunal ion and water absorption by endogenous angiotensin after dehydration
Authors: Levens N. R.
Published: December 2017

In the pentobarbital sodium-anesthetized rat, dehydration for 24 h increased ion and water absorption from the jejunum. Dehydration also elevated plasma concentrations of angiotensin peptides and plasma renin activity but did not significantly alter plasma aldosterone concentrations. Infusion of tyramine, norepinephrine, and angiotensin II (AII) also stimulated jejunal absorption in a manner similar to dehydration. The elevation of jejunal absorption in response to dehydration is totally inhibited by the converting enzyme inhibitor captopril and the angiotensin receptor antagonist [lle7]AIII. Thus, increased jejunal absorption following dehydration is mediated by the renin-angiotensin system and is not secondary to either aldosterone or to antidiuretic hormone release. Further experiments demonstrated that the increase in jejunal absorption in response to dehydration was unaffected by propranolol but was totally abolished by phentolamine, prazosin, and peripheral sympathectomy. It is proposed that AII stimulates jejunal absorption by enhancing transepithelial transport processes and/or by altering the balance of Starling forces governing fluid absorption across enteric capillaries. Angiotensin thus appears to be a physiologically important mediator of jejunal absorption in states characterized by extracellular volume depletion.
Central representation of arrival of nutrient in the duodenum
Authors: Ewart W. R. , Wingate D. L.
Published: December 2017

This study was carried out to assess the extent to which the appearance of a nutrient (D-glucose) in the duodenum of the anesthetized rat is signaled within the medulla. Recordings were made from single neurons in the region of the dorsal vagal nucleus and the nucleus tractus solitarius during constant single-pass perfusion of the duodenum with isotonic saline or D-glucose at 37 degrees C. In some experiments, the response of medullary neurons to acute gastric distension was also recorded. Of the 41 spontaneously firing neurons that were studied, 20 showed changes in firing rate when glucose replaced saline in the duodenal perfusate, 9 showed decreasing firing rates, and 11 showed increased firing rates. The spontaneous firing rate of glucose-sensitive neurons was significantly slower than that of glucose-insensitive neurons. In 14 neurons tested with both glucose perfusion and gastric distension, 6 responded to only one of the two stimuli, while only 2 responded to both. It is clear that the arrival of nutrient within the duodenum is rapidly signaled within the central nervous system, suggesting the possibility of neural as well as humoral modulation of the physiological changes seen on feeding.
Gastric surface cell function: potential difference and mucosal barrier
Authors: McGreevy J. M.
Published: December 2017

Rabbit fundic mucosa mounted in Ussing chambers for 4 h developed morphological deterioration of the gastric glands (GG), while the surface epithelial cell layer (SEC) remained intact. Since the tissues maintained a steady-state potential difference (PD) and resistance (R), it seemed that the surface cells might be responsible for both the PD and the R. To test this hypothesis, segments of fundic mucosa were exposed to selective anoxia by bubbling the mucosal (anoxic SEC) or serosal (anoxic GG) nutrient solutions with N2 instead of O2. Control tissues received O2 into both nutrient solutions. SEC anoxia resulted in a PD and short-circuit current (Isc) of zero within 10 min; R fell by 60% within 2 h. GG anoxia caused no change in PD or R over 2 h. Unidirectional fluxes (J) of 36Cl did not diminish as expected in tissues with no PD or Isc. This persistent JCl in tissues with a PD of zero was investigated in tissues with anoxic SEC. Simultaneous unidirectional fluxes of 36Cl and [3H]mannitol were determined to identify the transcellular (JClcell) and paracellular (JClleak) components of JCl during SEC anoxia. Similar flux measurements were made in control tissues (no anoxia). In control tissues, the calculated JClcell correlated with Isc (r = 0.72, n = 44). In tissues with anoxic SEC, the JClcell was 0.05 +/- 0.4 (mean +/- SD, n = 44). This series of experiments suggests that the PD and mucosal barrier characteristics of rabbit gastric mucosa in Ussing chambers are functions of a healthy surface cell layer.
Gastric mucosal protection with chronic mild restraint: role of endogenous prostaglandins
Authors: Wallace J. L. , Cohen M. M.
Published: December 2017

The role of endogenous prostaglandins (PGs) in adaptation of the rat gastric mucosa to chronic stress was examined. After 10 days of chronic mild restraint (CMR), gastric mucosal damage induced by orally administered 40% ethanol was significantly (P less than 0.01) less extensive than that to control mucosae. When the mucosal injury was produced by oral administration of acetylsalicylic acid (250 mg/kg), there was no protection afforded by prior exposure to CMR. Pretreatment with indomethacin (1 mg/kg ip) abolished the protective effects of CMR against ethanol injury. The indomethacin blockade of CMR protection was reversed by the subsequent administration of PGE2 (75 micrograms/kg po). Fundic samples from 10-day CMR rats synthesized three times as much PGE2 (P less than 0.01) and twice as much 6-keto-PGF1alpha (P less than 0.05) as control samples. Thromboxane B2 synthesis by control and CMR samples was not significantly different. The capacity of gastric fundus and antrum to synthesize PGE2 in vitro was higher in samples from CMR rats than from controls. These results suggest that the resistance to gastric injury that develops during chronic stress is mediated by endogenous prostaglandins.
Activities and subcellular localizations of enzymes implicated in gastroduodenal bicarbonate secretion
Authors: Stiel D. , Murray D. J. , Peters T. J.
Published: December 2017

Analytical subcellular fractionation of tissue whole homogenates and microanalysis of organelle marker enzymes were used to study the activity and subcellular localization of enzymes implicated in HCO3 secretion in rat duodenal and gastric antral mucosae. The following organelles, characterized by their marker enzymes, were located in the density gradients: cytosol (lactate dehydrogenase), plasma membrane (5'-nucleotidase), peroxisomes (catalase), mitochondria (succinate dehydrogenase), endoplasmic reticulum (Tris-resistant alpha-glucosidase), lysosomes (N-beta-acetylglucosaminidase), and brush-border membrane (Zn2+-resistant alpha-glucosidase and alkaline phosphatase). Compared with gastric antrum, rat duodenal mucosa contained over twice the activity of HCO3-ATPase and of Na+-K+-ATPase but less than one-tenth the activity of carbonic anhydrase. Duodenal HCO3-ATPase activity was observed in both mitochondrial and brush-border membrane fractions, whereas antral HCO3-ATPase activity was confined to mitochondria. Na+-K+-ATPase activity was found largely in the basolateral membrane (duodenum) and plasma membrane (antrum). In both tissues carbonic anhydrase activity was localized to the cytosolic fraction. These observations offer further evidence that differing biochemical mechanisms underlie HCO3 secretion by gastric and duodenal epithelia.
Cholera-induced mucin secretion from rat intestine: lack of effect of cAMP, cycloheximide, VIP, and colchicine
Authors: Roomi N. , Laburthe M. , Fleming N. , Crowther R. , Forstner J.
Published: December 2017

Purified cholera enterotoxin (20-50 micrograms) and dialyzed cholera filtrate (50-125 mg) increased net glycoprotein synthetic and secretory rates in rat intestinal epithelium. Specific goblet cell mucin secretion was increased 5- to 10-fold. However, other agents that increase intestinal cAMP and accelerate glycoprotein synthesis did not enhance mucin secretion. This was true for dibutyryl cAMP (10(-3) and 10(-2) M) with or without theophylline (10(-3) M) and isoproterenol (10(-4) M) with or without dibutyryl cAMP (10(-3) M). Hyperosmotic mannitol (450 mosmol/l), which increases fluid secretion but does not affect cAMP, and vasoactive intestinal peptide (2 X 10(-7) M), which increases both fluid secretion and cAMP, both failed to increase mucin secretion, implying that fluid "washout" of mucin adherent to the mucosal surface is not responsible for cholera-induced mucin secretion. Cycloheximide, an inhibitor of cholera diarrhea in vivo (20 mg/kg) or in vitro (1 mM), effectively abolished [3H]leucine incorporation into protein but did not affect cholera-induced mucin secretion. Colchicine (10-50 mg/kg) given to block microtubule assembly was similarly without effect on mucin secretion. These findings suggest that there is a dissociation of electrolyte/fluid and mucin secretory processes and cast doubt on the widely accepted notion that all cholera effects are mediated via the well-known adenylate cyclase-cAMP mechanism.
Gastroduodenal alkaline response to acid and taurocholate in conscious dogs
Authors: Konturek S. J. , Bilski J. , Tasler J. , Laskiewicz J.
Published: December 2017

Alkaline secretion was measured in the fundic and antral portions of the stomach and in the upper and distal portions of the duodenum in conscious dogs under basal conditions, in response to luminal exposure of HCl and taurocholate, and after feeding. Topical application of HCl (6.7-100 mM) resulted in an increase in HCO-3 output, particularly from the upper duodenum, and this was associated with the rise in prostaglandin (PG) E2 release. Since both these effects were abolished by pretreatment with indomethacin, it was concluded that the stimulation of alkaline secretion by topical HCl is mediated by mucosal PGs. HCl instilled into the main stomach or feeding a meat meal also caused an increase in alkaline secretion from the isolated (non-acid-perfused) gastric and duodenal portions, but this effect was not affected by indomethacin, suggesting that it was not mediated by endogenous PGs. Direct exposure of the mucosa to luminal taurocholate (0.62-20 mM) adjusted to pH 6.0 also increased gastroduodenal HCO-3 output, but this effect was not affected by indomethacin and accompanied by a fall in transmucosal PD value, suggesting that it could be due to the damage of the mucosa and increased mucosal permeability to HCO-3. We conclude that gastroduodenal HCO-3 output increases in response to natural substances such as HCl, taurocholate, or feeding, and the mechanism of this increase differs depending on the stimulant used.