Roles of in vitro - and in vivo -administered histamine and serotonin in compound 48/80-induced gastric acid secretion in isolated, perfused rat stomach

In this investigation, an isolated, perfused rat stomach system was used to elucidate the roles of histamine, serotonin, and the action of cimetidine, methysergide, and propranolol in relation to thein vivo andin vitro administration of compound 48/80. While histamine administered bothin vivo andin vitro stimulated acid secretion in the perfused rat stomach, serotonin, addedin vitro, inhibited histamine-induced gastric acid secretion. Cimetidine, given eitherin vivo orin vitro, blocked histamine-induced acid secretion, and methysergide, but not propranolol, reversed the serotonin-induced inhibition of histamine-stimulated acid secretion. Compound 48/80, givenin vitro, caused gastric acid secretion that was blocked by pretreatment with cimetidine. Administeredin vivo, however, compound 48/80 inhibited both basal and histamine-stimulated acid secretion. This inhibition was partially reversed by pretreatment with methysergide. The absence of inhibition of acid secretion byin vitro-administered compound 48/80 may be related to the timing of the serotonin effect. When serotonin was given prior to histamine, it blocked acid secretion, whereas no inhibition occurred when serotonin was administered together with histamine. None of the other agents investigated affected basal acid secretion.