Comparative Evaluation of the Role of Endogenous Gastrin in Basal Acid Secretion in Conscious Rats Provided with Chronic Fistula and Pylorus Ligation

• Published in: Japanese journal of pharmacology Vol. 71; no. 3; pp. 223 - 230
• Main Authors: Nishida, Akito, Uchida-Kobayashi, Ayumi, Takemoto, Yukihiro, Akuzawa, Shinobu, Miyata, Keiji
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Pharmacological Society 1996
• Subjects: Animals; Atropine - pharmacology; Basal acid secretion; Benzodiazepines - pharmacology; Cholinergic neuron; Chronic Disease; Famotidine - pharmacology; Gastric Acid - metabolism; Gastric Fistula - metabolism; Gastrin receptor; Gastrins - physiology; Histamine - physiology; Histamine H2-receptor; Ligation; Male; Parasympathetic Nervous System - physiology; Pylorus; Rats; Rats, Sprague-Dawley; YM022; Basal acid secretion; Cholinergic neuron; Histamine H2-receptor; Gastrin receptor; YM022
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.71.223

We determined the relative contributions of endogenous gastrin, histamine and cholinergic tone to basal acid secretion in chronic fistula rats. Results were compared with those for acid secretion in pylorus-ligated rats. In chronic fistula rats, YM022 {(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea} dose-dependently inhibited pentagastrin-stimulated acid secretion and abolished this secretion at 1 μmol/kg, s.c., but did not affect histamine- and carbachol-induced acid secretion even at 10 μmol/kg. In contrast, famotidine at 1 μmol/kg completely inhibited not only the acid secretion induced by histamine but also those by pentagastrin and carbachol. Furthermore, atropine abolished carbachol- and pentagastrin-stimulated acid secretion and significantly suppressed histamine-stimulated acid secretion at 0.1 μmol/kg. YM022 dose-dependently inhibited basal acid secretion. The YM022 dosage required to inhibit basal acid secretion is consistent with that required to suppress pentagastrin-induced acid secretion. Famotidine (1 μmol/kg) and atropine (0.1 μmol/kg) also abolished basal acid secretion. In pylorus-ligated rats, YM022 inhibited acid secretion in a dose-dependent manner; the inhibition at 1 μmol/kg, i.v. was 65%. No additional effect was observed when rats were dosed at 30 μmol/kg. Famotidine partially inhibited acid secretion in these rats, whereas atropine abolished this secretion. These results indicate that the major part of basal acid secretion in rats is attributable to endogenous gastrin via histamine- and cholinergic tone-dependent pathways. Moreover, pylorus ligation reduces the relative contribution of gastrin to acid secretion due to the activation of cholinergic tone.