Mechanism of oleic acid-induced inhibition on gastric acid secretion in rats

1991 ◽  
Vol 260 (4) ◽  
pp. G564-G570 ◽  
Author(s):  
J. C. Rhee ◽  
T. M. Chang ◽  
K. Y. Lee ◽  
Y. H. Jo ◽  
W. Y. Chey
Keyword(s):  
Oleic Acid ◽  
Acid Secretion ◽  
Peptide Yy ◽  
Acid Output ◽  
Inhibitory Effect ◽  
Rabbit Serum ◽  
Similar Degree ◽  
Normal Rabbit Serum ◽  
Anesthetized Rats ◽  
Acid Acid

We investigated the existence of an enterogastrone in rats induced by duodenal administration of oleic acid. Acid secretion by the luminally perfused stomach was stimulated in anesthetized rats by intravenous infusion of 0.3 micrograms.kg-1.h-1 pentagastrin. Intraduodenal administration of 3 mmol of oleic acid produced a profound inhibition (94%) of pentagastrin-stimulated acid output in 10 rats (P less than 0.01). Of several peptides in plasma including secretin, neurotensin, somatostatin, and peptide YY, only secretin was found to increase significantly (P less than 0.001). A similar degree of inhibition of acid output (93%) was caused by porcine secretin, 5.6 pmol.kg-1.h-1, given intravenously to mimic the plasma level of secretin produced by oleic acid infusion. The inhibitory effect of oleic acid on the acid secretion was completely reversed by intravenous injection of a rabbit antisecretin serum but not by a normal rabbit serum. These observations strongly suggest that the inhibition was mediated via circulating secretin. The inhibition produced by either oleic acid or secretin was completely blocked by indomethacin. The blocking action was completely reversed by intravenous administration of 48 micrograms.kg-1.h-1 prostaglandin E2. We conclude that endogenous secretin is a major enterogastrone released by oleic acid in anesthetized rats and that the inhibitory action of secretin requires endogenous prostaglandins.

Role of vagal and splanchnic capsaicin-sensitive afferents in enterogastric inhibition of acid secretion in rats

1995 ◽  
Vol 268 (2) ◽  
pp. G286-G291
Author(s):  
E. Saperas ◽  
J. Santos ◽  
J. R. Malagelada
Keyword(s):  
Acid Secretion ◽  
Acid Output ◽  
Inhibitory Effect ◽  
Intestinal Perfusion ◽  
Neural Pathways ◽  
Anesthetized Rats ◽  
Antisecretory Effect ◽  
Bilateral Vagotomy ◽  
Celiac Ganglionectomy

The role of capsaicin-sensitive afferent innervation and neural pathways involved in the enterogastric inhibition of gastric acid secretion by luminal acid was investigated in urethan-anesthetized rats. Intestinal perfusion with graded concentrations of HCl (50, 75, and 100 mM) for 1 h dose dependently inhibited both thyrotropin-releasing hormone (TRH) analogue- and pentagastrin-stimulated acid output (P < 0.01). The inhibitory effect of intestinal perfusion with HCl (100 mM) on pentagastrin-stimulated acid secretion was blocked by bilateral vagotomy, whereas celiac ganglionectomy had no effect. Systemic capsaicin pretreatment (125 mg/kg sc) reduced the antisecretory effects of luminal acid on both TRH analogue- and pentagastrin-stimulated acid secretion. Neither selective perivagal nor selective periceliac capsaicin treatments (1% solution) modified the antisecretory effect of intestinal perfusion with HCl (75 mM) on TRH analogue-stimulated acid secretion. However, combined selective perivagal plus periceliac capsaicin treatment reduced it to the same extent as systemic capsaicin treatment. We conclude that enterogastric inhibition of acid secretion by luminal acid in urethan-anesthetized rats is mediated by extrinsic reflexes involving both vagal and splanchnic capsaicin-sensitive afferent fibers.

Inhibitory effect of PYY on vagally stimulated acid secretion is mediated predominantly by Y1 receptors

1996 ◽  
Vol 270 (1) ◽  
pp. G123-G127 ◽  
Author(s):  
K. C. Lloyd ◽  
D. Grandt ◽  
K. Aurang ◽  
V. E. Eysselein ◽  
M. Schimiczek ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Peptide Yy ◽  
Acid Output ◽  
Inhibitory Effect ◽  
Acid Inhibition ◽  
Molecular Forms ◽  
Gastric Fistula ◽  
Selective Agonist ◽  
Rabbit Intestine ◽  
Y1 Receptors

Two molecular forms of peptide YY (PYY), PYY-(1--36) and PYY-(3--36), are abundant in rabbit intestine and blood. We have previously shown that PYY-(1--36) (PYYI) activates equipotently Y1 and Y2 receptors and PYY-(3--36) (PYY II) is a highly selective agonist for Y2 receptors. In the present study, we examined the effect of exogenous infusion of PYY on vagally stimulated gastric acid secretion in awake rabbits with chronic gastric fistula. To determine the specific PYY receptor(s) that mediates this effect, we used a highly selective Y1 agonist, Pro34-PYY, a synthetic PYY, and a Y2-selective agonist, PYY II. Vagal stimulation of acid secretion was elicited by an intravenous bolus injection of insulin (0.125 U/kg) 30 min after beginning a 180-min intravenous infusion of either PYY I, PYY II, or [Pro34]-PYY after a 50 micrograms/kg i.v. bolus of atropine followed immediately by a 500 micrograms/kg sc injection. During infusion of 200 pmol.kg 1.h-1 PYY I, acid output was significantly inhibited to 45 +/- 13% of maximum acid output 60 min after injection of insulin. Similarly, acid output during infusion of 200 pmol.kg-1.h-1 [Pro34]-PYY was significantly inhibited to 52 +/- 12% of maximum. In contrast, acid output during infusion of 200 pmol.kg-1.h-1 of PYY II was not significantly inhibited (101 +/- 18% of maximum). Infusion of double the dose (400 pmol.kg-1.h-1) of PYY II resulted in acid inhibition (51 = 15% of maximum), whereas infusion of the same dose did not significantly enhance acid inhibition by infusion of either PYY I or [Pro34]-PYY (28 +/- 11 and 42 +/- 15% of maximum). These results indicate that PYY, acting predominantly at Y1 receptors, is a potent inhibitor of vagally stimulated acid secretion in adult rabbits.

Role of gastrin, histamine, and acetylcholine in the gastric phase of acid secretion in anesthetized rats

1992 ◽  
Vol 262 (4) ◽  
pp. G747-G755 ◽  
Author(s):  
K. C. Lloyd ◽  
H. E. Raybould ◽  
Y. Tache ◽  
J. H. Walsh
Keyword(s):  
Monoclonal Antibody ◽  
Acid Secretion ◽  
Acid Output ◽  
Inhibitory Effect ◽  
Gastric Distension ◽  
Plasma Gastrin ◽  
Titratable Acid ◽  
Anesthetized Rats ◽  
Dependent Pathway

To determine the relative contributions of gastrin, histamine, and cholinergic stimulation to the gastric phase of acid secretion, peptone-stimulated acid output was measured in urethan-anesthetized pylorus-ligated rats after intravenous administration of gastrin monoclonal antibody, cimetidine, and atropine. Intragastric peptone stimulated acid secretion four-fold over basal, which was associated with a significant increase in plasma gastrin levels. Gastrin immunoneutralization and simultaneous H2- and muscarinic-receptor blockade demonstrated that approximately 40% of peptone-stimulated acid output as attributed to endogenous gastrin through a histamine-dependent pathway, whereas 20% of acid output was accounted for by a cholinergic component. Another 10% of titratable acid was omeprazole-insensitive and presumably due to intragastric digestion of peptone. Therefore, approximately 30% residual acid output in response to peptone could not be accounted for by known acid stimulatory mechanisms. In rats given somatostatin monoclonal antibody to block the tonic inhibitory effect of endogenous somatostatin, residual acid output was a similar fraction of meal-stimulated acid output. In contrast, gastric distension induced by intragastric instillation of saline stimulated acid secretion to 1.5-fold over basal. Although 60% of distension-induced acid secretion could be inhibited by either H2 blockade or gastrin immunoneutralization, acid output returned to basal levels after simultaneous muscarinic blockade. These results indicate that gastrin, through a histaminergic pathway, is the principal mediator of meal-stimulated acid secretion in anesthetized rats. Approximately 30% of acid output was due to other unidentified mechanisms, such as chemical secretagogues, a direct effect of amino acids, or novel peptides.

scholarly journals MEK inhibits secretin release and pancreatic secretion: roles of secretin-releasing peptide and somatostatin

2001 ◽  
Vol 280 (5) ◽  
pp. G890-G896 ◽  
Author(s):  
James P. Li ◽  
Kae Yol Lee ◽  
Ta-Min Chang ◽  
William Y. Chey
Keyword(s):  
Pancreatic Secretion ◽  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Pancreatic Exocrine Secretion ◽  
Pancreatic Fluid ◽  
Pancreatic Exocrine ◽  
Small Intestinal ◽  
Secretin Release

We investigated the mechanism of action of methionine enkephalin (MEK) on HCl-stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats with pancreatobiliary cannulas and isolated upper small intestinal loops were perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were diverted. The effect of intravenous MEK on acid-stimulated secretin release and pancreatic exocrine secretion was then studied with or without coinfusion of naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid perfusate, which contains secretin-releasing peptide (SRP) activity, was collected from donor rats with or without pretreatment with MEK, MEK + naloxone, or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused intraduodenally into recipient rats. MEK increased plasma SS concentration and inhibited secretin release and pancreatic fluid and bicarbonate secretion dose-dependently. The inhibition was partially reversed by naloxone and anti-SS serum but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin level and pancreatic secretion. CAP SRP bioactivity decreased when it was collected from MEK-treated donor rats; this was partially reversed by coinfusion with naloxone or anti-SS serum. These results suggest that in the rat, MEK inhibition of acid-stimulated pancreatic secretion and secretin release involves suppression of SRP activity release. Thus the MEK inhibitory effect appears to be mediated in part by endogenous SS.

scholarly journals Intestinal fat-induced inhibition of meal-stimulated gastric acid secretion depends on CCK but not peptide YY

1999 ◽  
Vol 276 (2) ◽  
pp. G550-G555 ◽  
Author(s):  
Xiao-Tuan Zhao ◽  
John H. Walsh ◽  
Helen Wong ◽  
Lijie Wang ◽  
Henry C. Lin
Keyword(s):  
Small Intestine ◽  
Gastric Emptying ◽  
Acid Secretion ◽  
Receptor Antagonist ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Peptide Yy ◽  
Inhibitory Effect ◽  
Proximal Half

Fat in small intestine decreases meal-stimulated gastric acid secretion and slows gastric emptying. CCK is a mediator of this inhibitory effect (an enterogastrone). Because intravenously administered peptide YY (PYY) inhibits acid secretion, endogenous PYY released by fat may also be an enterogastrone. Four dogs were equipped with gastric, duodenal, and midgut fistulas. PYY antibody (anti-PYY) at a dose of 0.5 mg/kg or CCK-A receptor antagonist (devazepide) at a dose of 0.1 mg/kg was administered alone or in combination 10 min before the proximal half of the gut was perfused with 60 mM oleate or buffer. Acid secretion and gastric emptying were measured. We found that 1) peptone-induced gastric acid secretion was inhibited by intestinal fat ( P < 0.0001), 2) inhibition of acid secretion by intestinal fat was reversed by CCK-A receptor antagonist ( P < 0.0001) but not by anti-PYY, and 3) slowing of gastric emptying by fat was reversed by CCK-A antagonist ( P< 0.05) but not by anti-PYY. We concluded that inhibition of peptone meal-induced gastric acid secretion and slowing of gastric emptying by intestinal fat depended on CCK but not on circulating PYY.

Candidate canine enterogastrones: acid inhibition before and after vagotomy

1997 ◽  
Vol 272 (5) ◽  
pp. G1236-G1242 ◽  
Author(s):  
K. C. Lloyd ◽  
S. Amirmoazzami ◽  
F. Friedik ◽  
A. Heynio ◽  
T. E. Solomon ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Peptide Yy ◽  
Acid Output ◽  
Gastric Fundus ◽  
Acid Inhibition ◽  
Selective Vagotomy ◽  
Before And After ◽  
Calculated Dose ◽  
Vagal Innervation ◽  
Glucagon Like Peptide 1

The relative contributions of several gut-derived peptides as enterogastrones known to be released in response to a fatty meal and to inhibit acid secretion have not previously been compared directly. We determined the acid-inhibitory activities of increasing intravenous doses of several peptides before and after highly selective vagotomy (HSV) during intragastric titration of a peptone meal in dogs. Before HSV, threshold inhibitory doses of peptide YY (PYY), cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg-1.h-1, respectively, whereas neurotensin, glucagon-like peptide-1 (GLP-1), and oxyntomodulin failed to inhibit acid secretion at doses up to 1,000 pmol.kg-1.h-1. The calculated dose producing 50% acid inhibition (ID50) of secretin (62 pmol.kg-1.h-1) was one-half that of PYY (128 pmol.kg-1.h-1). Maximal (90%) acid inhibition was produced by 100 pmol.kg-1.h-1 secretin and 500 pmol.kg-1.h-1 PYY. The highest dose of CCK that did not cause vomiting (100 pmol.kg-1.h-1) inhibited peptone-stimulated acid output by only 60%. After HSV, 500 pmol.kg-1.h-1. PYY and 200 pmol.kg-1.h-1 CCK failed to inhibit acid output by more than 50%. Threshold doses for inhibition by PYY and CCK were 200 and 100 pmol.kg-1.h-1, respectively. Secretin remained a potent inhibitor after HSV, with an ID50 of 80 pmol.kg-1.h-1 and a threshold dose of 10 pmol.kg-1.h-1. HSV also failed to affect inhibition caused by somatostatin. This study has shown that PYY and secretin are somewhat more potent and efficacious inhibitors of acid secretion than CCK but that all three peptides are far more active than GLP-1, neurotensin, and oxyntomodulin. PYY and CCK inhibit acid secretion in large part through vagal innervation of the gastric fundus, but the inhibitory effects of secretin are independent of fundic vagal innervation.

Cocaine- and amphetamine-regulated transcript peptide attenuates phenylephrine-induced bradycardia in anesthetized rats

2003 ◽  
Vol 285 (6) ◽  
pp. R1496-R1503 ◽  
Author(s):  
Phouangmala Scruggs ◽  
Siok L. Dun ◽  
Nae J. Dun
Keyword(s):  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Solitary Tract ◽  
Peptide Fragment ◽  
Tract Tracing ◽  
Anesthetized Rats ◽  
Nodose Ganglia ◽  
Cart Peptide ◽  
Resting Blood Pressure

The present study was undertaken to investigate the origin of cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactive (irCART) fibers observed in the nucleus of the solitary tract (NTS) and assess the role of CART peptide on phenylephrine (PE)-induced baroreflex. Immunohistochemical and retrograde tract-tracing studies showed that some of the irCART fibers observed in the NTS may have their cell bodies in the nodose ganglia. In urethane-anesthetized rats, intracisternal or bilateral intra-NTS microinjection of the CART peptide fragment 55-102 (0.1-3 nmol), referred to herein as CARTp, consistently and dose dependently attenuated PE-induced bradycardia. CARTp, in the doses used here, caused no significant changes of resting blood pressure or heart rate. Bilateral intra-NTS injections of CART antibody (1:500) potentiated PE-induced bradycardia. Injections of saline, normal rabbit serum, or concomitant injection of CARTp and CART antiserum into the NTS caused no significant changes of PE-induced baroreflex. The result suggests that endogenously released CARTp from primary afferents or exogenously administered CARTp modulates PE-induced baroreflex.

scholarly journals Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain

2000 ◽  
Vol 279 (3) ◽  
pp. G575-G581 ◽  
Author(s):  
Hong Yang ◽  
Keishi Kawakubo ◽  
Helen Wong ◽  
Gordon Ohning ◽  
John Walsh ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Peptide Yy ◽  
Vagal Stimulation ◽  
Inhibitory Effect ◽  
Supporting Evidence ◽  
Intracisternal Injection ◽  
Site Of Action ◽  
The Brain

The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59 ± 7 μmol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol · kg−1 · h−1 PYY, respectively. PYY or PYY3–36 (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY3–36 by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol · kg−1 · h−1). When injected intracisternally, the PYY antibody (280 μg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol · kg−1 · h−1)-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain.

Endogenous prostaglandins in gastric alkaline response in the rat stomach after damage

1986 ◽  
Vol 250 (6) ◽  
pp. G842-G849 ◽  
Author(s):  
K. Takeuchi ◽  
S. Ueki ◽  
H. Tanaka
Keyword(s):  
Acid Secretion ◽  
Functional Recovery ◽  
Inhibitory Effect ◽  
Similar Degree ◽  
Common Phenomenon ◽  
Rat Stomach ◽  
Concurrent Administration ◽  
Prostaglandin Biosynthesis ◽  
Endogenous Prostaglandins

A role of endogenous prostaglandins in gastric alkaline response (an increase of luminal pH) and functional recovery was investigated in the rat stomach after damage with acidified taurocholate (TC, 20 mM) or aspirin (ASA, 40 mM). Exposure of the stomach to TC or ASA similarly produced a transmucosal potential difference (PD) reduction and enhancement of H+ backdiffusion. The PD was restored gradually with time, and this process was much faster in the case of TC compared with ASA. After exposure to TC, acid secretion ceased and bicarbonate (0.5–1 mu eq/10 min) appeared in the lumen, whereas acid secretion persisted in the stomach exposed to ASA. However, in the presence of cimetidine (8 mg . kg-1 . h-1), these two agents produced a similar degree of luminal alkalinization (approximately 1 mu eq/10 min of HCO3-). Pretreatment with indomethacin (5 mg/kg, sc) significantly inhibited luminal alkalinization and PD recovery seen after exposure to TC. Concurrent administration of 16,16-dimethyl prostaglandin E2 (3 micrograms/kg, sc) antagonized the effects of indomethacin in stomachs exposed to TC and also unmasked luminal alkalinization and expedited the PD recovery in stomachs exposed to ASA. The levels of PGE2 and 6-keto-PGF1 alpha in the corpus mucosa were significantly increased in stomachs exposed to TC, but decreased in those exposed to ASA. These results indicate that luminal alkalinization of the stomach after damage with TC results from both an inhibition of acid secretion caused by endogenous prostaglandins and an increased appearance of HCO-3, and may play a role in functional recovery of the damaged mucosa. Gastric alkalinization seems to be a common phenomenon after exposure to mucosal damaging agents unless they have an inhibitory effect on prostaglandin biosynthesis.

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