peptones and gastrin-17

Gastrin has a potent influence on gastric acid secretion and mucosal growth but its role in mucosal integrity has been little studied. This study investigated in rats whether gastrin protects the gastric mucosa against the damage by 100% ethanol and what are the possible mechanisms of this protection. Exogenous gastrin-17 (0.6-5.0 pmol/kg) injected subcutaneously (s.c.) reduced dose dependently ethanol-induced mucosal damage and the dose decreasing the ethanol lesions by 50% was about 1.8 pmol/kg. The protection afforded by gastrin-17 was accompanied by a dose-dependent increase in gastric blood flow and these effects were almost completely abolished by the pretreatment with specific CCKB (L-365,260) but not CCKA receptor antagonist (loxiglumide). Endogenous gastrin released by intragastric (i.g.) peptone meal or s.c. injection of gastrin-releasing peptide prevented the formation of acute ethanol-induced lesions and these effects were also abolished by the pretreatment with L-365,260 but not by loxiglumide. The inhibition of nitric oxide (NO) synthase, by NG-nitro-L-arginine methyl ester almost completely eliminated both the protective and hyperemic effects of gastrin-17 and the addition of L-arginine (but not D-arginine) to NG-nitro-L-arginine-methyl ester restored, in part, these effects of gastrin-17. Deactivation of sensory nerves with capsaicin did not influence the protective or hyperemic effects of gastrin-17. We conclude that both exogenous and endogenous gastrin exert its protective activity against ethanol damage of gastric mucosa and this effect is mediated through the interaction with specific CCKB receptors and arginine-NO pathway, but does not involve sensory nerves.

Topics: Animals; Aspirin; Capsaicin; Dinoprostone; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Male; Neurons, Afferent; Nitric Oxide; Peptides; Peptones; Rats; Rats, Wistar; Stomach Diseases

With the availability of selective gastrin/CCKB (L365,260) and CCKA (L364,718) receptor antagonists the present study was designed to investigate the role of gastrin and cholecystokinin (CCK) receptors in meal-stimulated gastric acid secretion. Gastric acid output was measured by continuous intragastric titration in conscious rats. Vehicle (dimethylsulfoxide/saline, 3:1), L365,260 (3 or 9 mg/kg), or L364,718 (1 mg/kg) was given by i.v. bolus injection. Basal acid output was strongly inhibited by both doses of L365,260 while L364,718 had no effect. Intragastric peptone (4%, w/v) increased acid secretion 40-65% of the response to a maximal dose (2.5 nmol/kg per h) of gastrin-17. L365,260 completely abolished gastrin-17 stimulated acid secretion and partially inhibited peptone-induced acid secretion. Blockade of CCKA receptors by L364,718 did not affect peptone-stimulated acid output. This study demonstrates that gastrin/CCKB receptors are important in regulating basal acid secretion in the conscious rat while CCKA receptors do not appear to influence basal or peptone-stimulated gastric acid secretion. Blockade of gastrin/CCKB receptors partially inhibits intragastric meal-stimulated acid secretion indicating that the gastrin/CCKB receptor has a physiological role as mediator of food-stimulated acid secretory response in conscious rats.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Eating; Gastric Acid; Gastrins; Hormones; Injections, Intravenous; Male; Peptones; Phenylurea Compounds; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

Gastrin 17-I was infused into conscious rats equipped with jugular and portal vein catheters and with a pyloric gastric drainage tube to achieve serum concentrations slightly higher than those found during intragastrically instilled peptone solutions. I.v. injected rabbit gastrin antiserum abolished gastrin 17-I-stimulated gastric acid secretion in these animals. Gastrin immunoneutralization reduced peptone-stimulated gastric acid secretion by approximately 37% during the entire 30-min period of stimulation. Peptone-stimulated gastric acid secretion was only significantly (P less than 0.05) inhibited in the third 10-min period, but not in the first or second 10-min periods of stimulation. This study demonstrates that the late but not the initial period of peptone-stimulated gastric acid secretion is regulated by circulating gastrin in rats.

Topics: Animals; Gastric Acid; Gastrins; Immune Sera; Male; Peptones; Rats; Rats, Inbred Strains

We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg.h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg.h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients.

Topics: Animals; Antibodies, Monoclonal; Dogs; Gastric Acid; Gastrins; Glucose; Histamine; Hormones; Isotonic Solutions; Neutralization Tests; Peptones

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Topics: Adult; Aged; Duodenal Ulcer; Evaluation Studies as Topic; Food; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Glucose; Humans; Infusions, Parenteral; Male; Middle Aged; Peptones; Sodium Chloride; Time Factors

Studies were performed in six men to determine the relationship between serum gastrin concentration and gastric function during exogenous and endogenous stimulation of gastrin release. When the intragastric pH was maintained at 5.0, there were dose-related increases in gastric acid secretion with increasing serum gastrin concentrations produced either by stepwise increasing doses of intravenous gastrin or bombesin, or by intragastric perfusion with peptone. When intragastric pH was maintained at 2.5, or when intravenous atropine was given hourly, sensitivity to both exogenous and endogenously released gastrin were similarly decreased. Gastric emptying was inhibited in a dose-dependent manner by both bombesin and peptone but not by exogenous gastrin. These results suggest that bombesin and peptone stimulate gastric acid secretion through release of circulating gastrin but inhibit gastric emptying by another mechanism.

Topics: Adult; Aged; Bombesin; Dose-Response Relationship, Drug; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Middle Aged; Peptides; Peptones