Effect of histamine on gastric acid secretion “in vitro”: Interference with endogenous prostaglandins

Abstract

The interference between histamine and endogenous prostaglandins (PGs) was investigated in the isolated gastric fundus from immature rats by evaluating the effect of nonsteroidal antiinflammatory agents (NSAIDs) on the acid response to histamine and the effect of histamine on PGs production by the gastric mucosa. Indomethacin (10(-5) M) and diclofenac (10(-5) M) caused a dose-dependent enhancement of the response to histamine, dimaprit and DBcAMP, but did not affect bethanechol-, isoprenaline- and forskolin-induced acid production. The enhancing effect of indomethacin was abolished in low Ca2+ medium. PGE2 and 6-keto PGF1 alpha levels in the mucosal solution were not modified by histamine, while being reduced by indomethacin. From these data it is concluded that endogenous PGs may negatively modulate the secretory response to histamine. However, a direct effect of the amine on cyclooxygenase to increase PGs synthesis seems to be excluded since histamine did not modify PGs levels in the mucosal solution.

CYCLO‐OXYGENASE‐1 INHIBITION INCREASES ACID SECRETION BY MODULATING H+,K+‐ATPase EXPRESSION AND ACTIVATION IN RABBIT PARIETAL CELLS

“…Of note, certain NSAIDs, such as diclofenac and piroxicam, while inhibiting prostaglandin synthesis also inhibit isolated gastric gland acid secretion by interacting with H + /K + ‐ATPase activity 13 . We and others have observed that NSAIDs stimulate basal acid secretion in vivo 7,10,11,14 and potentiate secretagogue‐stimulated acid secretion in vitro and in vivo 6,8,9,15,16 . A rational approach to prevent ulcerogenesis is to suppress the production of gastric acid, either with histamine H 2 receptor antagonists or proton pump inhibitors.…”

“…13 We and others have observed that NSAIDs stimulate basal acid secretion in vivo 7,10,11,14 and potentiate secretagogue-stimulated acid secretion in vitro and in vivo. 6,8,9,15,16 A rational approach to prevent ulcerogenesis is to suppress the production of gastric acid, either with histamine H 2 receptor antagonists or proton pump inhibitors. The latter have been shown to prevent the relapse of endoscopic ulcers in patients receiving long-term therapy with NSAIDs or COX-2 inhibitors.…”