Effect of histamine on gastric acid secretion "in vitro": interference with endogenous prostaglandins.

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.