Pavlov Pouch Research Articles

Changes of Gastric Secretion after Bolus and Slow Intravenous Administration of Bombesin and Neurotensin

Objectives:The aim of the present study was to evaluate the changes caused by intravenous administration of regulatory peptides, bombesin (BBS) and neurotensin (NT), on gastric secretion, serum gastrin, and plasma levels of bombesin-1ike immunoreactivity (BLI) and neurotensin. Materials and methods: Fourteen dogs underwent an upper gastrointestinal tract operation and a Pavlov pouch for the concentration of gastric fluids was formed. The experimental animals were divided into two groups. Peptides were given one month after the second operation and after fasting for 12 hours. In group A, the effects of BBS were studied after a rapid 1 ìg/kg body weight dose and a slow 30´ 0.5 ìg/kg body weight dose administration intravenously. Correspondingly to group B the effects of NT were studied in the same way. Results:The rapid intravenous infusion of BBS caused a very significant increase in gastrin levels, BLI in plasma, volume and HCl of the gastric fluids. The same results, plus a significant decrease in gastric pH, were observed following slow intravenous infusion of BBS. Concerning the NT, rapid administration caused a significant decrease in the volume of gastric fluids. Slow NT administration of caused a significant reduction in gastric fluid volume and in HCl. On the contrary, pH was significantly increased. Conclusion:Bombesin increases plasma gastrin levels and HCl secretion. Neurotensin administration causes a decrease in HCl secretion without affecting gastrin levels in plasma.

M2042 Adaptive and Median Signal Filtering to Reduce Vascular and Respiration Artifacts in High-Resolution Esophageal Pressure Topography (HREPT) Studies

truncal vagotomized dogs. The concentration of serum 5-Hydroxytryptamine (5-HT) were measured before and after intragastric administration of MSG.MSG solution was administered into the stomach before feeding and gastric emptying was evaluated. Several antagonists were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (which was a vagally innervated corpus pouch), Heidenhain (which was a vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Results: Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG did not induce a specific pattern such as an increase or decrease of serum 5-HT. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. Moreover, intragastric and intraduodenum MSG at a dose of 90 mM/kg mostly induced retrograde migrating contractions in the jejunum, which propagated to the gastric body and were followed by vomiting. The MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, granisetron, and dopamine. The gut motility was increased by intrapouch injection of MSG in Pavlov pouch, but it was not affected in Heidenhain or antral pouch. Conclusions: Intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve.

Intragastric monosodiuml-glutamate stimulates motility of upper gut via vagus nerve in conscious dogs

Monosodium l-glutamate (MSG) is a substance known to produce the umami taste. Recent studies indicate that MSG also stimulates a variety of activities in the gastrointestinal tract through its receptor in the gut, but no study has reported the activity in conscious large experimental animals. The aim of our study was to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Contractile response to intraluminal injection of MSG was studied in the fed and fasted states by means of chronically implanted force transducers. MSG (5, 15, 45, and 90 mM/kg) dissolved in water was injected into the stomach and duodenum in normal and vagotomized dogs. MSG solution was administered into the stomach before feeding, and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and granisetron) were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (vagally innervated corpus pouch), Heidenhain (vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, and granisetron. Gut motility was increased by intrapouch injection of MSG in the Pavlov pouch, but it was not affected in the Heidenhain or antral pouch dogs. We conclude that intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve.

Effect of Free Dietary Glutamate on Gastric Secretion in Dogs

The amino acid, L-glutamate, which is abundant in many foodstuffs, is a potent stimulator of gastric vagal afferents. The aim of the study was to evaluate a role of dietary glutamate in neuroendocrine control of gastric secretion of acid, pepsinogen, and fluid. In mongrel dogs with small gastric pouches surgically prepared according to Pavlov (vagally innervated) or Heidenhain (vagally decentralized), secretion in a pouch was induced by infusion into the main stomach of an amino acid-rich diet lacking glutamate (Elental) or the same diet supplemented with monosodium glutamate (MSG). Having no effect alone, MSG (100 mM) potentiated secretion induced by Elental both in Pavlov and Heidenhain models. In the Pavlov pouch, the effect of MSG was markedly reduced after i.v. injection of granisetron, an antagonist of 5-HT(3) receptors. In the Heidenhain model, MSG enhanced the stimulatory effect of pentagastrin (1 microg/kg, s.c.). In conclusion, dietary glutamate at doses not exceeding its common concentrations in foods substantially potentiates gastric phase secretion induced by stimulation of gastric mucosa with an amino acid-rich diet or by administration of pentagastrin. The effect of glutamate is partially mediated via serotonin secretion and stimulation of 5-HT(3) receptors.

Dietary monosodium glutamate enhances gastric secretion

Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT(3) receptors in the gastric mucosa.

Peptide YY(1-36) and Peptide YY(3-36): Part II. Changes after Gastrointestinal Surgery and Bariatric Surgery: Part I. Distribution, Release and Actions appeared in the last issue (May 2006)

Peptide YY (PYY) is secreted as a 36 amino acid, straight chain polypeptide, and is found in greatest concentrations in the terminal ileum, colon and rectum. After secretion, dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal Tyrosine-Proline residues from PYY(1-36), producing PYY(3-36). PYY(1-36) acts at all four human Y receptors, Y1, Y2, Y4 and Y5, while PYY(336) is a specific Y2 receptor agonist. PYY participates in the regulation of appetite and weight balance through hypothalamic-based mechanisms. PYY(1-36) stimulates appetite and weight gain through Y1 and Y5 receptors. PYY(3-36) suppresses appetite and stimulates weight loss through Y2 receptors. GI diseases that cause malabsorption increase both basal and meal-stimulated PYY levels. In contrast, obesity decreases both basal and meal-stimulated PYY levels. Mutations in the human PYY and Y2 receptor genes may contribute to the development of obesity. Small bowel resection elevates PYY levels in humans. Colon resections increase PYY levels in animal models but not in man. PYY changes following bariatric operations are incompletely studied. Vertical banded gastroplasty, open Roux-en-Y gastric bypass and jejunoileal bypass significantly elevate basal and meal-stimulated PYY levels. In dogs with Pavlov pouches, Roux-en-Y duodenojejunostomy (duodenal switch) increases PYY levels compared to Roux-en-Y gastrojejunostomy. DPP-IV activity is increased in obese individuals and remains increased after biliopancreatic diversion. Thus, diseases or operations which cause malabsorption, elevate basal and meal-stimulated PYY levels. Bariatric operations also increase basal and meal-stimulated PYY levels. This suggests that the combination of increased PYY levels and elevated levels of DPP-IV observed after bariatric operations may generate increased circulating levels of PYY(3-36), leading to hypothalamic-mediated suppression of appetite and promotion of weight loss through Y2 receptor mediated mechanisms.

Effect of peptide YY on gastric motor and secretory activity in vagally innervated and denervated corpus pouch dogs

In this study, we examined the mechanism by which constant intravenous infusion of physiological doses of PYY affects gastric secretion and motility in the vagally innervated (Pavlov) and denervated (Heidenhain) corpus pouch. As a result, only in the Heidenhain pouch, PYY at a dose of 100 pmol/kg-h significantly inhibited gastric secretion in the interdigestive and postprandial states. A dose of 300 pmol/kg-h inhibited the gastric secretion in both types of pouch, but inhibition in the Pavlov pouch was less than in the Heidenhain pouch. The inhibitory effect of PYY on phase III contractile activity was dose-dependent and significant, except in the Heidenhain pouch, and no dose of PYY had any effect on postprandial gastric motility. After all, vagal denervation enhanced the inhibitory effect of PYY on gastric secretion, but abolished the inhibitory effect on phase III contractile activity. Our findings strongly suggest that the inhibitory effect of PYY on gastric secretion is in part mediated by a non-vagal pathway and the inhibitory effect of PYY on gastric motor activities is completely dependent on vagal innervation, but the vagus nerve acts as an inhibitory modulator of the inhibitory effect of PYY on gastric secretion.

Inhibition of phase III activity by acidifying stomach in vagally denervated and innervated dogs with gastric pouches

Background/Aims: Intragastric acidification at pH 1.0 strongly inhibits phase III contractions in the dog, but this mechanism is not well known. We studied the mechanism in conscious dogs. Methods: Vagally denervated and innervated gastric pouch dogs were prepared. Force transducers were chronically implanted on the serosa of the pouch, main stomach, and midduodenum. The pH of the perfusate was monitored. Results: Administration of histamine (40 μg · kg−1 · h−1 intravenously [IV]) and instillation of acidic saline at pH 1.0, but not pH 2.0, into the main stomach strongly inhibited the motilin-induced (0.1 μg/kg IV) phase III activity in the main stomach and the innervated pouch but did not influence contractions in the extrinsically denervated pouch. Famotidine completely reversed the histamine-induced inhibition of phase III in the main stomach and Pavlov pouch. Acidification of the pouch itself or duodenum at pH 1.0 did not affect contractions in the main stomach and pouch of either type. Conclusions: The mechanism of inhibition of motilin-induced phase III activity by acid in the stomach involves the intact vagovagal reflex, but sympathetic participation is not completely ruled out. The inhibition of motilininduced phase III activity may originate in the antral mucosa of the stomach.

Intracerebroventricular infusion of neurotensin suppresses gastric acid secretion in dogs.

Synthetic neurotensin (NT) was infused intracerebroventricularly in 14 mongrel dogs to study the effects of the peptide on gastric secretion and on gastrin and NT levels. The infusion was performed with a specific apparatus, and gastric fluid was collected with a Pavlov pouch. NT was given in two series of experiments: as a bolus intracerebroventricular injection of 269.8 pmol/kg and as a continuous intracerebroventricular infusion at a rate of 539.6 pmol/kg/h for 30 min. The bolus injection caused a very significant decrease of gastric fluid volume, a significant decrease of HCl output and a significant increase of its pH, while serum immunoreactive gastrin increased significantly. The continuous infusion of NT caused similar changes in gastric secretion. The plasma NT levels did not change. In conclusion, the intracerebroventricular administration of NT increases the serum gastrin levels, decreases the volume and HCl content of gastric fluid, and increases its pH.

Gastric Antisecretory Activity of 15(R)-15-Methylprostaglandin E2, Arbaprostil, in Dogs.

The gastric antisecretory activity of 15(R)-15-methylprostaglandin E2 (arbaprostil) was compared with that of natural prostaglandin (PG) E2 in Pavlov pouch dogs. Arbaprostil significantly inhibited pentagastrin- and food-stimulated gastric secretion when it was administered directly into the pouch at a dose of 10-30 micrograms/pouch and 30-300 micrograms/pouch, respectively. Natural PGE2, however, was inactive up to 1000 micrograms/pouch. The data indicate that arbaprostil is a potent, long-acting orally active antisecretory drug that may be useful for the treatment of peptic ulcer disease.

Gastric Antisecretory Activity of 15(R)-15-Methylprostaglandin E2, Arbaprostil, in Dogs

The gastric antisecretory activity of 15(R)-15-mcthylprostaglandin E2 (arbaprostil) was compared with that of natural prostaglandin (PG) E2 in Pavlov pouch dogs. Arbaprostil significantly inhibited pentagastrin- and food-stimulated gastric secretion when it was administered directly into the pouch at a dose of 10-30 μg/pouch and 30-300 μg/pouch, respectively. Natural PGE2, however, was inactive up to 1000 μg/pouch. The data indicate that arbaprostil is a potent, long-acting orally active antisecretory drug that may be useful for the treatment of peptic ulcer disease.

CHANGES IN GASTRIC ACID SECRETORY ACTIVITY DURING THE INTERDIGESTIVE STATE IN THE DOG

The relationship between acid secretion, interdigestive migrating contractions (IMC) in the stomach, and gastrointestinal hormones in the dog was investigated. Heidenhain pouches and Pavlov pouches were perfused with saline (1.3 ml/min) and pH changes in the perfusate were recorded continuously by means of an indwelling pH sensor. Force transducers were used to detect contractions. The pH value started to increase 3.2min after a bolus injection of cimetidine, and decreased 3.1min after the administration of betazole hydrochloride. Seventy percent of all registered IMC cycles obtained from Pavlov pouch dogs showed a decrease in pH values from 4.2±0.1 to 1.7±0.1 (mean±S.E.) corresponding to phase II contractile activity. The other 30% of the cycles did not demonstrate any changes in pH value. Acid outputs during 10min, including the minimum pH value, were 29.9±4.6% of those observed 30-40min after feeding. The decrease in pH values during phase II was also recognized in Heidenhain pouch dogs. The serum gastrin concentration during the pH-decreasing phase (40.8±4.5pg/ml) was significantly higher (p<0.05) than that in the pH-increasing phase (23.0±3.4), and significantly lower (p<0.01) than that (141 8±10.6) obtained at 30min after feeding. The serum concentration of motilin during the pH-decreasing period (265.3±49.3pg/ml) was significantly lower (p<0. 05) than that during the increasing phase (430.8±34.3). Administration of exogenous motilin induced phase III-like contractile activity and significantly elevated the pH value from 3.9±0. 1 to 4.6 ± 0.3. Cimetidine increased pH values significantly from 4.0 ± 0.3 to 5.5 ± 0.1 (p<0. 01), and the duration of an IMC cycle (101.8±4.5min) was not significantly different from that of the control (103.5±6.5). These data indicate that a simple device used in these experiments detects changes in acid secretory activity in the canine gastric pouch within 3 min. Acid secretion during fasting is activated in association with phase II contractile activity in 70% of IMC cycles in the stomach. Gastrin and motilin are likely to be involved in controlling the activity. The H2 receptor blocker (cimetidine) suppresses acid secretion during phase II, but does not affect the IMC cycle.

Changes in Gastric Secretion after Intracerebroventricular Infusion of Bombesin in Dogs

Synthetic bombesin (BBS) was infused intracerebroventricularly in 14 mongrel dogs, to study the effects of the peptide on gastric secretion and on gastrin and neurotensin levels. The infusion was performed with a specific apparatus, and gastric fluid was collected with a Pavlov pouch. BBS was given in two series of experiments: as a bolus intracerebroventricular injection of 308.6 pmol/kg and as a continuous intracerebroventricular infusion at a rate of 617.3 pmol/kg/h for 30 min. The bolus injection caused a very significant decrease of gastric fluid volume, a significant decrease of HCl output, and a significant increase of its pH, while serum immunoreactive gastrin increased significantly. The continuous infusion of BBS caused similar changes in gastric secretion. The plasma neurotensin levels did not change. In conclusion, the intracerebroventricular administration of BBS increases the serum gastrin levels, decreases the volume and HCl content of gastric fluid, and increases its pH.

Gastrin and somatostatin in the rat antrum. The effect of removal of acid-secreting mucosa

Female rats were subjected to operations aimed at reducing the amount of oxyntic gland mucosa draining its acid secretion to the antrum. The rats were provided either with Heidenhain or Pavlov pouches reducing the oxyntic mucosa draining its secretion to the antrum by about 50% or subjected to various degrees (75, 90 and 100%) of fundectomy. Ten weeks following surgery, plasma levels of gastrin and somatostatin were assayed. At the same time, antral mucosal content of gastrin and somatostatin was determined as well as the mucosal density of these hormone-producing cells. There was a relationship between the amount of acid-secreting mucosa removed and the ensuing plasma concentration of gastrin. Thus, a stepwise increase in plasma gastrin was found with the highest levels obtained in rats subjected to 90 or 100% fundectomy. The somatostatin concentration in plasma was reduced only in rats subjected to fundectomy with the most sustained decrease in animals in which all oxyntic gland mucosa had been removed. There was also a relationship between the amount of acid-secreting mucosa removed and the gastrin content of the antral mucosa. An inverse relationship seemed to exist between antral gastrin and somatostatin concentrations. However, a significant decrease in somatostatin concentration of the antral mucosa was seen only in rats subjected to a fundectomy. The number of gastrin cells in the antral mucosa was increased in fundectomized rats only, with the largest density seen in rats deprived of all oxyntic mucosa. A corresponding decrease in the number of somatostatin cells was noticed. Our results would suggest an apparent functional relationship between antral gastrin and somatostatin cells, where the antral acid load (or pH) appears to be the major factor of physiological significance.

Experimental evaluation of staple lines in gastric surgery.

This study was designed to evaluate the bursting pressure, tensile strength, and healing of staple lines in the dog stomach. Pavlov pouches were created in 30 dogs using a single, double, or triple application of a stapler loaded with 4.8-mm staples. Staple lines were assessed immediately in half of the animals and after 21 days in the remaining animals. Acutely, reinforcing a single staple line with a second or third application of the stapler resulted in an anastomosis more resistant to leakage and disruption. Satisfactory healing occurred by 21 days and contributed to staple line strength in the pouches using a single and double application of the stapler. The orientation of collagen deposition in the anastomosis was related to the number of staples used. The degree of collagen deposition across the muscularis mucosa correlated with the healed staple line strength. Although healing occurred when a triple application of the stapler was utilized, the orientation of the fibroconnective tissue was parallel to the anastomosis and did not contribute to staple line integrity.

Influence of Antacids on the Gastric Antisecretory Activity of the Synthetic Prostanoid (8R,11R,12S,15R,5Z,13E)-15-(Acetyloxy)-11,16,16-trimethyl-9-oxoprosta-5,13-dien-1-oic Acid in Dogs

Liquid antacids that contain aluminium–magnesium hydroxides reduce the absorption of various therapeutic agents. To assess the potential for such an interaction with the synthetic anti-ulcer prostanoid (8R, 11R, 12S, 15R, 5Z, 13E)-15-(acetyloxy)-11, 16, 16-trimethyl-9-oxoprosta-5, 13-dien-1-oic acid (1; Ro 22-6923), we studied the effect of Mylanta and DiGel liquid on the gastric antisecretory activity of this drug in dogs. Dogs were prepared with a modified Pavlov (innervated) pouch. Compound 1 was administered alone or with liquid antacid into the main stomach while acid secretion into the pouch was measured. Mylanta (30mL) and DiGel (35mL) failed to significantly reduce the ability of 1 (0.5mg/kg, orally) to inhibit histamine (25 μg/kg/h)-stimulated secretion. Neither the onset nor the duration of action of 1 was affected by either antacid. The total acid output over the 4h after administration of 1 was not significantly affected by the antacids. The results suggest that Mylanta and DiGel, or antacids of a composition similar to that of these products, are not likely to interfere with the antisecretory activity of 1 in humans.

Effect of proglumide on gastrointestinal motility and gastric secretion in the conscious state.

Proglumide suppressed neither phase III activity nor propagation of interdigestive migrating contractions (IMC) in the gastrointestinal tract. Furthermore, proglumide did not inhibit the gastric motor activity stimulated by pentagastrin, however, it suppressed the pH in Pavlov pouch stimulated by pentagastrin in the interdigestive state. On the contrary, in the digestive state, proglumide did not suppress the pH. That might be due to not only various gut hormones including gastrin, but also neural stimulation, mechanical stimulation and so on. In conclusion, antigastrin effect of proglumide is rather remarkable on the acid secretion not on the gastrointestinal motor activity. Proglumide may be an antacid without suppression of motor activity.

Cell loss from human, canine and guinea-pig gastric mucosa measured by DNA radioimmunoassay

A DNA radioimmunoassay, sensitive in the range 25-1000 ng, has been developed to measure gastric mucosal cell loss. Validity of the assay was based on antibody specificity, absence of interference from gastric contents, parallel tracer displacement by dilutions of gastric and standard DNA, and crossover with colorimetric assay. With this assay, gastric DNA shedding was examined in two animal species and man. In the guinea-pig stomach, DNA loss was 20-100 micrograms/h and in the canine Pavlov pouch, 260-580 micrograms/h. In the canine Pavlov pouch stimulation of acid secretion by histamine and exposure to exogenous acid increased DNA output. In the normal human stomach DNA loss was 544 +/- 175 micrograms/h and in duodenal ulcer patients, 649 +/- 225 micrograms/h. DNA radioimmunoassay provides a sensitive and reproducible measure of cell exfoliation from the stomach and may be a useful tool for studying aspects of gastric mucosal defence.

Effect of intraantral and intrabulbar pH on somatostatin-like immunoreactivity in peripheral venous blood of conscious dogs. The possible function of somatostatin as an inhibitory hormone of gastric acid secretion and its possible identity with bulbogastrone and antral chalone.

The aim of the present study was to investigate whether circulating somatostatin takes part in the inhibition of gastric acid secretion induced by acidification of the antrum and the duodenal bulb. Dogs provided with chronic pouches of the antrum or the duodenal bulb, and with Pavlov pouches were used in the study. Peripheral venous somatostatin levels rose on the average to ˜36±15 pmol/1 and 20±3 pmol/1 during perfusion of the antral or bulbar pouches with 0.1 M HC1 respectively. A slight increase was also obtained on antral perfusion with solutions of pH 2.2–3 and on bulbar perfusion with solutions of pH 2.2, whereas peripheral somatostatin levels remained unchanged, when the pouches were exposed to solutions of higher pH. The increase of plasma somatostatin levels coincided in time with the release of somatostatin into the lumen of the antrum and of the duodenal bulb, which showed the same pH dependency. Also plasma gastrin levels rose during perfusion of the pouches with 0.1 M HCI, this was especially the case during perfusion of the antral pouches. Perfusion of bulbar pouches, but not of antral pouches with 0.1 M HC1 inhibited the pentagastrin (2 μg/kg/h) stimulated gastric acid secretions. Infusions of somatostatin (0.15, 0.3 and 0.6 nmol/kg/h) caused plasma somatostatin levels ˜0, 0–20 and ˜50 pmol/1 respectively. Infusions of somatostatin (0.3‐1.2 nmol/kg/h) inhibited pentagastrin stimulated (2 μg/kg/h) gastric acid secretion and 0.15 nmol/kg/h inhibited the acid secretion induced by pentagastrin (1 μg/kg/h). Thus infusions of somatostatin which inhibited pentagastrin induced acid secretion gave rise ot plasma somatostatin levels of comparable size ˜(0–50 pmol/1) to those induced by acidification of the antrum or the duodenal bulb ˜(36 and 20 pmol/1). We therefore suggest that endogenously released somatostatin may account for the inhibition of gastric acid secretion observed during acidification of the duodenal bulb, thus corresponding to the postulated hormone bulbogastrone. The existence of similar inhibitory substance of antral origin (i. e. the antral chalone) has been proposed. We also suggest that this substance corresponds to somatostatin, despite the fact that it is difficult to inhibit pentagastrin‐induced gastric acid secretion by acidification of the antrum. It is suggested that the inhibitory effect on gastric acid secretion exerted by somatostatin released from the antrum might be masked under the present experimental conditions. Thus, gastrin and perhaps also other peptides, which stimulate acid secretion, are also released by antral acidification and they might in part counteract the depressant effect on acid secretion induced by somatostatin. Furthermore, since the antral pouches were innervated, vagovagal reflexes induced by antral acidification might also influence the rate of acid secretion. The main physiological function of the acid induced antral somatostatin release might be to block the release of gastrin in response to various stimuli.

Feeding and depression of abomasal secretion in sheep elicited by elfazepam and 9- aza-cannabinol

Elfazepam (7-chloro-1-[2-(ethylsulfonyl)ethyl]-5-(2-fluorophenyl)-1,3-dihydro- 2H-1,4benzodiazepin-2-one) and- 9-aza-cannabinol (10-hydroxy-β-(3-methyl-2-octyl)-5′,5-dimethyl-5H-1 benzopyranol 3,4-d pyridine, HCl) were administered IV to study their effects on feed intake and acid secretion in abomasal Pavlov pouches in sheep. Elfazepam and 9-aza-cannabinol increased 3-fold 3 hr postinjection feed intake and decreased abomasal acid secretion compared to saline and DMSO (dimethyl sulfoxide) control treatments. At doses which elicit feeding, 9-aza-cannabinol was a much more potent inhibitor of acid secretion than elfazepam. These results are consistent with the theory of localized hypothalamic nuclei which have roles in the control of both feed intake and gastric acid secretion. However, in contrast to feeding associated with normal hunger, the benzodiazepine and cannabinol stimulated feeding is associated with decreased gastric acid secretion.