The antigastrinic effect of a phenothiazine (LM 24056) prevents gastric secretory activity of histamine.

Gastric antisecretory phenothiazine LM 24056 inhibited acid and pepsin responses to feeding in dogs. Administered perorally two hours before feeding, LM 24056 reduced significantly the secretory responses to combinations of feeding either with antramine, a natural histamine derivate, or with synthetic histamine. LM 24056 reduced circulating gastrin levels (p less than 0.01 and p less than 0.001) and gastrin responses to feeding (p less than 0.01) without modifying neither circulating histamine concentrations nor histamine responses to feeding. The residual acid and pepsin secretions were closely related to gastrin reduction and endogenous or exogenous histamine, by themselves, seemed to be unable to recover the levels of secretory responses observed in response to feeding alone or in combination with antramine or histamine. These data favour a new scheme of gastric secretion regulation where gastrin would be the last step for stimulating parietal and chief cells. LM 24056 by reducing circulating gastrin prevents stimulatory effect of exogenous or feeding-released endogenous histamine. Histamine would not be thus the final common mediator for gastric secretion.