Interaction of prostaglandins and histamine with enzymes of cyclic AMP metabolism from guinea pig gastric mucosa.

Abstract

A B S T R A C T Prostaglandins (PGEi, PGE2, PGA1) and histamine have opposing effects on gastric HCl secretion, but we found that both stimulate adenylate cyclase activity in cell-free membrane preparations of guinea pig gastric fundic mucosa. The stimulatory effect of prostaglandins was found in this study to be specific and dose-dependent over a concentration range from 10' to 10-' M. In similar preparations from antral regions of guinea pig gastric mucosa, the adenylate cyclase was stimulated only by PGE1, PGE2, and PGA1 and not by histamine. Maximum stimulating doses of PGE,, PGE2, or PGAi, and of histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. Metiamide, a histamine H2-receptor antagonist, inhibited the stimulation of fundic mucosa adenylate cyclase by histamine but did not interfere with the stimulation by prostaglandins. Cyclic AMP phosphodiesterase activity of guinea pig gastric mucosa was unaffected by PGE, and PGE2 or by histamine, and was slightly depressed by PGAi. These results indicate that histamine and prostaglandins stimulate two different adenylate cyclase systems both present in guinea pig gastric mucosa tissue. Therefore, the known inhibitory effect of prostaglandins on gastric acid secretion is not related to the interference with the stimulation of the histamine H2-receptor-sensitive adenylate cyclase complex by histamine nor do prostaglandins accelerate cyclic AMP This work was presented in part at the

Specific inhibition by prostaglandins E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic adenosine monophosphate generation by isolated canine parietal cells.

“…In the present study, both PGE2 and PGI2, acting in the absence of histamine, stimulated cyclic AMP production. However, in accord with the findings in intact mucosa (20,21,28), stimulation of cyclic AMP production was only found at concentrations of the prostaglandins >1 ,ulM and such high concentrations are unlikely to occur in vivo even under extreme conditions (29). Furthermore, PGE2 appears to stimulate cyclic AMP production primarily in mucosal cells other than parietal cells themselves.…”

“…Furthermore, Glick (40) demonstrated that PGE, inhibited histamine-but not carbachol-stimulated chloride transport by polarized isolated parietal cells. The view that prostaglandins inhibit histamine-stimulated cyclic AMP production was not widely accepted both because the role of cyclic AMP as a mediator of histamine action on the parietal cell was highly disputed (41), and because prostaglandins were shown to stimulate, not inhibit adenylate cyclase in gastric mucosa (20,21). However, this latter effect of prostaglandin occurs only with micromolar concentrations of prostaglandins both in intact mucosa and with isolated cells.…”

“…Stimulation by histamine, but not by carbachol or gastrin, was found to be accompanied by increased parietal cell generation of cyclic AMP (19). Prostaglandin E2 (PGE2), which is known to stimulate cyclic AMP production by gastric mucosa (20,21), was found to increase cyclic AMP production predominantly in nonparietal cells, with at most a very small effect on parietal cells (22). These observations with isolated mucosal cells did not resolve the question of the relation, if any, between the effects of PGE2 on cyclic AMP production and inhibition of acid secretion by PGE2.…”

Selective inhibition by somatostatin of cyclic AMP production in rat gastric glands

“…10" M histamine, respectively (tig.lB). In accordance with [21], histamine had no effect on cyclic AMP production in gastric glands isolated from the antrum (table 1). In gastric fundus, the addition of somatostatin 10d M produced a 64 and 61% inhibition of the effect produced by 5 .…”

Gastric Mucosal Energy Metabolism in Stress Ulcer

“…Hypersecretion of histamine in gastric mucosa increases biosynthesis o f prostaglandins from arachidonic acid [4], Formation of prostaglandins is initiated by release o f unsaturated acids from the mem brane phospholipids due to activation o f local phospholipases [7], Prosta glandins PGE and PGA stimulate cyclic AMP in gastric mucosa [27], this effect being responsible for the cytoprotecting action o f prostaglandins against experimental ulcerative lesions. When there is a marked hypersecre tion of histamine, as occurs in restraint-induced ulcers, arachidonic acid cannot complete its metabolic cycle to form PGE and PGA.…”