Metiamide and stimulated acid secretion from the isolated non‐distended and distended mouse stomach.

Abstract

1. The action of metiamide, a specific histamine H2-receptor antagonist, on the acid secretary response to various gastric stimuli in the perfused isolated whole mouse stomach is described. 2. Two kinds of stomach preparations, the non-distended stomach and distended stomach, were used. The distended stomach gave a marked and dose-related acid secretary response to histamine (10-6 to 10-3 M), pentagastrin (10-8 to 10-5 M), acetylcholine (5 x 10-5 to 10-5 M), eserine (10-5 to 10-3 M) or dibutyryl cyclic AMP (5 x 10-5 to 10-3 M). In the non-distended stomach, dibutyryl cyclic AMP regularly stimulated acid secretion in a dose-dependent manner; in contrast to dibutyryl cyclic AMP, histamine, pentagastrin or acetylcholine did not always stimulate acid secretion. 3. Histamine or pentagastrin but not acetylcholine always caused significant stimulation of acid secretion from the non-distended stomach in the presence of a phosphodiesterase inhibitor such as caffeine, theophyl-line or the I.C.I. compound, 63197. At the concentration of 10-4 M, these phosphodiesterase inhibitors markedly potentiated the stimulatory effect of histamine or pentagastrin on acid secretion and the order of effectiveness was 63197 > theophylline > caffeine. 63197 also produced profound potentiation of histamine-or pentagastrin-stimulated acid secretion in the distended stomach. 4. Metiamide (5 x 10-5 M to 10-4 M) did not antagonize stimulation of acid secretion by dibutyryl cyclic AMP in the non-distended or distended stomach. 5. In the distended stomach, metiamide (5 x 10-5 M) produced significant inhibition of histamine-stimulated acid secretion with a linear and parallel displacement of the histamine dose-response curve to the right. Although at this concentration metiamide did not depress maximal acid secretary response to histamine, it caused marked reduction of the maximal acid secretary response attainable with pentagastrin. 6. In the distended stomach, metiamide (5 x 10-5 M) did not cause significant inhibition of acetylcholine-,i duced acid secretion. Atropine (5 X 10-6 M) abolished the stimulatory effect of acetylcholine; it also produced marked inhibition of pentagastrin-stimulated acid secretion but it had little effect on acid secretion induced by histamine. 7. The present results indicate that metiamide inhibited histamine-induced acid secretion by competitive antagonism of the histamine H2-receptor, but its inhibitory effect on pentagastrin-induced acid secretion seemed to be of non-competitive nature. The failure of metiamide to inhibit acid secretion induced by dibutyryl cyclic AMP suggests that cyclic AMP might regulate gastric acid secretion at a site beyond the histamine H2-receptor activation. It is also considered that the present results support the hypothesis that cyclic AMP may be involved in hist-amine-or pentagastrin-induced acid secretion in the isolated mouse stomach. 8. The physiological role of histamine and its possible interaction with other known gastric stimuli in the regulation of gastric acid secretion is dis...

The isolated stomach preparation of the mouse: a physiological unit for pharmacological analysis

“…Davenport & Chaure (1950) tried to improve delivery using hyperbaric oxygen. Wan (1977) found that mouse stomachs would only secrete when distended. All the preparations which secrete well, in vitro, have thin walls -immature rat stomachs, mature mouse stomachs, guinea-pig mucosal sheets.…”

“…However, in the last few years or so, it has become possible to measure the secretion of acid by the intact stomachs of mature mice (Wan, 1977;Angus & Black, 1978); by the intact stomachs of immature guinea-pigs (Spencer, 1974) and rats (Parsons, 1975); by the mucous membrane, separated as a sheet, from kittens (Tepperman et al, 1975) and piglets (Forte et al, 1975); and by mixed but enriched suspensions of separated oxyntic cells (Soil, 1977). In addition, some of the biochemical elements subserving acid secretion, such as the hormone-receptor coupled systems on the basal membranes (Scholes et al, 1976) and the H+/ K+-ATPase located on the apical membranes (Fellenius et al, 1981) are now available for pharmacological studies.…”

Comparative study of the control of basal acid output from rodent isolated stomachs

“…The isolated, lumen-perfused stomach of the mouse is now a standard preparation for studying the pharmacology of oxyntic cell secretion (Wan, 1977;Angus & Black, 1979;Szelenyi & Vergin, 1980;Mahklouf & Schubert, 1990). Under basal conditions, this preparation lowers the pH of the unbuffered perfusate from about 6.0 to about 4.4.…”

The effects of atropine and secoverine on gastric secretion and motility in the mouse isolated stomach

“…The effects of atropine and secoverine on bethanechol-induced gastric acid secretion and bethanechol-induced motility were investigated in vitro, using stomachs, removed from adult ASH/TO albino mice of either sex, weighing between 15 to 25 g. The technique was based on that described by Bunce &Parsons, (1976) andWan, (1977). All experiments were carried out on stomachs from two mice, one to measure secretion and the other motility.…”