Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats

1997 ◽  
Vol 272 (5) ◽  
pp. G1243-G1248 ◽  
Author(s):  
K. Aurang ◽  
C. F. Spraggs ◽  
C. Jordan ◽  
K. C. Lloyd
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Rat Model ◽  
Acid Output ◽  
Male Rats ◽  
Plasma Histamine ◽  
Plasma Gastrin

Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in vivo, intact, anesthetized rat model, we studied the role of gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine and somatostatin during intragastric stimulation of acid secretion during a peptone meal. In pylorusligated, adult male rats (each implanted with a gastric cannula and portal venous and splenic artery catheters), after a 30-min basal period, gastric acid secretion was stimulated for 90 min either by an intravenous infusion of gastrin-17 (15 micrograms.kg-1.h-1) or by extragastric titration of 5 ml 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous plasma gastrin, histamine, and somatostatin concentrations were measured before and after close-arterial injection of a new, relatively selective, gastrin/CCK-B receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and plasma somatostatin by 34%. During intragastric peptone meal stimulation GR143330X reduced the acid response by 42% during the 30- to 60-min period but not during the 60- to 90-min period. GR143330X reduced the plasma histamine response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block the gastrin response to peptone at any time. These results indicate that GR143330X is an effective agent for blocking gastrin-stimulated acid secretion and histamine and somatostatin release in rats. Furthermore, we show for the first time in an intact, in vivo, anesthetized rat model that meal-stimulated activation of gastrin/CCK-B receptors stimulates acid secretion in part by regulating the release of histamine and somatostatin.

Inhibition of bombesin-stimulated acid secretion by immunoneutralization of gastrin in dogs

1995 ◽  
Vol 268 (1) ◽  
pp. G54-G58
Author(s):  
T. O. Kovacs ◽  
K. C. Lloyd ◽  
H. Wong ◽  
J. H. Walsh
Keyword(s):  
Monoclonal Antibody ◽  
Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Gastric Fistula ◽  
Gastrin Release ◽  
Gastric Acid Output ◽  
Plasma Gastrin

Bombesin-like peptides stimulate gastrin release and gastric acid secretion. The increase in gastric acid output is thought to be secondary to gastrin release. A monoclonal antibody (MAb) directed specifically to gastrin (MAb 28.2) was used to study the role of circulating gastrin in the regulation of bombesin-stimulated acid secretion in dogs. Seven conscious, fasted dogs with gastric fistulas received intravenous bombesin infusions in fourfold increasing doses from 200 to 3,200 pmol.kg-1.h-1. Each dose was given for 45 min. On separate days, dogs were pretreated with an intravenous infusion of 7 mg of MAb 28.2 or vehicle (0.1% canine serum albumin). Samples of gastric effluent were collected by gravity drainage through the gastric fistula, and acid output was measured by titration of gastric effluent to pH 7.0, using 0.2 N NaOH. Plasma gastrin concentrations were determined by radioimmunoassay. Bombesin infusion produced dose-dependent increases in plasma gastrin concentrations and gastric acid output. Administration of gastrin MAb 28.2 abolished bombesin-stimulated gastric acid output. Immunoneutralization of circulating gastrin in vivo using a gastrin monoclonal antibody in dogs indicates that the acid stimulatory response to bombesin is mediated by gastrin.

Secretin: a physiological regulator of gastric emptying and acid output in dogs

1994 ◽  
Vol 267 (4) ◽  
pp. G702-G708 ◽  
Author(s):  
H. O. Jin ◽  
K. Y. Lee ◽  
T. M. Chang ◽  
W. Y. Chey ◽  
A. Dubois
Keyword(s):  
Amino Acid ◽  
Gastric Emptying ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Dose Range ◽  
Physiological Role ◽  
Plasma Gastrin

Secretin has been known to inhibit gastric acid secretion in several species. However, the physiological role of secretin on the postprandial acid output and gastric emptying in an intact stomach remains controversial. In the present study, we reinvestigated the role of secretin in physiological dose range and endogenous secretin on gastric acid secretion and emptying in the stomach without influencing intragastric luminal pH in dogs. In seven conscious dogs with gastric cannulas, a 4% amino acid meal was administered intragastrically, and three different doses of secretin and an antisecretin serum were infused intravenously in each dog on separate days. Gastric emptying and net acid output were measured using a dye dilution technique, and plasma secretin and gastrin were determined by specific radioimmunoassays. After the meal, gastric emptying was exponential: acid output peaked at 25 min, and plasma concentrations of gastrin and secretin peaked at 15 and 60 min, respectively. Intravenous infusion of secretin at 1.25, 2.5, and 5.0 pmol.kg-1.h-1 dose dependently increased plasma levels of the peptide and suppressed postprandial plasma gastrin response and gastric acid output and emptying of the meal. Immunoneutralization of circulating secretin with a rabbit antisecretin serum abolished the postprandial rise of plasma secretin and significantly increased plasma gastrin, and augmented gastric emptying as well as acid output. It is concluded that, in dogs, secretin plays a physiological role in the regulation of gastric emptying and acid output after a liquid amino acid meal and that these effects may be mediated in part by suppression of the release of gastrin.

Gastrin mediates the gastric mucosal proliferative response to feeding

1996 ◽  
Vol 271 (3) ◽  
pp. G470-G476 ◽  
Author(s):  
G. V. Ohning ◽  
H. C. Wong ◽  
K. C. Lloyd ◽  
J. H. Walsh
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Pancreatic Secretion ◽  
Proliferative Response ◽  
Male Rats ◽  
Oxyntic Mucosa ◽  
Proliferative Zone ◽  
Mucosal Proliferation

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.

scholarly journals Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole

Gut ◽  
1999 ◽  
Vol 44 (4) ◽  
pp. 468-475 ◽  
Author(s):  
D Gillen ◽  
A A Wirz ◽  
W D Neithercut ◽  
J E S Ardill ◽  
K E L McColl
Keyword(s):  
Helicobacter Pylori ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Intragastric Ph ◽  
Ammonia Production ◽  
Intragastric Acid ◽  
H Pylori

BACKGROUNDOmeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production byH pylori has been suggested as a probable mechanism.AIMSTo assess the effect ofH pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects.METHODSTwentyH pylori positive and 12H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured.RESULTSPrior to omeprazole, measurements were similar in the H pyloripositive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pyloripositive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia.CONCLUSIONThe presence ofH pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

The role of peripheral opioid receptor subtypes in the modulation of gastric acid secretion and plasma gastrin in dogs

1993 ◽  
Vol 243 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Luigi Intorre ◽  
Grazia Mengozzi ◽  
Elisabetta Vanni ◽  
Francesco Grassi ◽  
Giulio Soldani
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Opioid Receptor ◽  
Receptor Subtypes ◽  
Plasma Gastrin ◽  
Opioid Receptor Subtypes

Relationship between maternal milk PGE2 and gastric acid secretion in newborn rats

1990 ◽  
Vol 259 (5) ◽  
pp. G702-G708
Author(s):  
A. Wirbel ◽  
R. Ducroc ◽  
B. Garzon ◽  
C. Merlet-Benichou ◽  
J. P. Geloso
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Sesame Oil ◽  
Newborn Rats ◽  
Maternal Milk ◽  
Infant Rats

We previously demonstrated that in rats gastric acid secretion declines after birth and drops steeply on day 12 of life. In the present study, we investigated the part played in this decline by prostaglandin E2 (PGE2) from maternal milk. PGE2 content was first measured in the milk of untreated dams 0, 1, 5, 10, 12, 15, and 18 days after parturition. PGE2 levels were high during the first 5 days (123.5-200.5 pg/ml), declined significantly between days 10 and 15 (56.6-85.4 pg/ml; P less than 0.05), and dropped to 18.4 pg/ml on day 18. We also found that depleting milk of PGE2 prevented drop of acid secretion in 12-day-old suckling rats. Injecting lactating dams with indomethacin significantly reduced milk PGE2 content by 65% vs. milk of untreated dams. Surprisingly, administration of sesame oil, the indomethacin vehicle to the dams, increased milk PGE2 content by 182%. In the pups of the indomethacin-treated dams, acid secretion did not drop. On the contrary, in vivo basal and histamine-induced acid output rose markedly by 40 and 50%, respectively, and in vitro the net movements of 36Cl and 22Na measured in the isolated stomach indicated that active Cl- secretion had resumed. Mucosal PGE2 did not appear to be significantly involved in early development of acid secretion because administration of indomethacin to pups from untreated dams did not significantly modify the secretion measured on day 12. Data indicate that maternal milk depletion of PGE2 prevents the drop of gastric acid secretion previously observed in 12-day-old pups and suggest that in infant rats maternal PGE2 plays a physiological part in regulating acid secretion.

Tonic suppression of gastric acid secretion by endogenous peptides in neonatal rats

1995 ◽  
Vol 269 (5) ◽  
pp. G721-G728
Author(s):  
R. K. Rao ◽  
S. Pepperl ◽  
F. Porreca
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Neonatal Rats ◽  
In Vitro Techniques ◽  
Basal Acid ◽  
Old Rats

Stimulation of gastric acid secretion by secretagogues was measured in developing rats by in vivo and in vitro techniques. Basal acid outputs in vivo were very low in 8- and 14-day-old rats compared with those in 20- and 30-day-old rats. In 20-day-old rats, all secretagogues increased acid output in vivo, whereas only carbachol, pentagastrin, and sulfated cholecystokinin octapeptide (CCK-8S) were active in 14-day-old rats. In contrast, basal acid output in vitro and stimulation by secretagogues did not differ significantly with age. CCK-8S-stimulated acid output in vitro in 14-day-old rats was blocked by L-365,260, L-364,718, tetrodotoxin, and atropine, but not by hexamethonium, whereas gastrin-stimulated acid output was blocked only by L-365,260. Furthermore, acid output in vivo was elevated three- to fourfold by subcutaneous naloxone-methiodide or L-364,718, but not by L-365,260, in 14-day-old rats; none of these antagonists produced an effect in 20-day-old rats. These studies show that low basal gastric acid output in neonatal rats is caused by tonic inhibitory regulation by endogenous regulatory peptides.

scholarly journals Role of ghrelin in the regulation of gastric acid secretion involving nitrergic mechanisms in rats

2008 ◽  
pp. 563-568
Author(s):  
HM Bilgin ◽  
C Tumer ◽  
H Diken ◽  
M Kelle ◽  
A Sermet
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Output ◽  
Control Group ◽  
Albino Rats ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Plasma Nitrite

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), has been identified in the rat and human gastrointestinal tract. Ghrelin has been proposed to play a role in gastric acid secretion. Nitric oxide (NO) was shown as a mediator in the mechanism of ghrelin action on gastric acid secretory function. However, there is a little knowledge about this topic. We have investigated the role of ghrelin in gastric acid secretion and the role of NO as a mediator. Wistar albino rats were used in this study. The pyloric sphincter was ligated through a small midline incision. By the time, saline (0.5 ml, iv) was injected to the control group, ghrelin (20 μg/kg, iv) was injected to the first experimental group, ghrelin (20 μg/kg, iv) + L-NAME (70 mg/kg, sc) was injected to the second group and L-NAME (70 mg/kg, sc) was administered to the third group. The rats were killed 3 h after pylorus ligation; gastric acid secretion, mucus content and plasma nitrite levels were measured. Exogenous ghrelin administration increased gastric acid output, mucus content and total plasma nitrite levels, while these effects of ghrelin were inhibited by applying L-NAME. We can conclude that ghrelin participates in the regulation of gastric acid secretion through NO as a mediator.

Achlorhydria-induced hypergastrinaemia: the role of bacteria

1991 ◽  
Vol 80 (4) ◽  
pp. 281-284 ◽  
Author(s):  
J. Calam ◽  
R. A. Goodlad ◽  
C. Y. Lee ◽  
B. Ratcliffe ◽  
M. E. Coates ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Gastrin Release ◽  
Plasma Gastrin ◽  
H2 Receptor Antagonist ◽  
Histamine H2 Receptor ◽  
Germ Free ◽  
Dose Dependent

1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 ± 11 pmol/l (mean ± SEM) and 36 ± 8 pmol/l, respectively, after vehicle, and 153 ± 30 pmol/l and 181 ± 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day−1 kg−1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day−1 kg−1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 ± 11 pmol/l), but further elevated plasma gastrin concentrations to 278 ± 26 pmol/l in conventional rats (P <0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.

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