The secretory actions of histamine in rat small intestine.

1. Histamine caused a dose-dependent rise in the transintestinal potential difference in vivo that was competitively blocked by H1, but not by H2 antagonists. This effect of histamine was also reduced by the cyclo-oxygenase inhibitor indomethacin. 2. Histamine induced a net secretion of fluid by the small intestine and this effect was reduced by indomethacin. 3. In intestinal sheets histamine increased the potential difference, short-circuit current and tissue resistance. This response was decreased in the absence of Cl- and in the presence of furosemide, suggesting that Cl- secretion was responsible for the observed electrical changes. This was confirmed by direct measurement of ion fluxes which showed an increase in net Cl- secretion together with an inhibition of net Na+ absorption. 4. The response to histamine was Ca2+-dependent since it was inhibited by removal of serosal Ca2+ and by verapamil. 5. Indomethacin caused a dose-dependent reduction in the response of intestinal sheets to histamine, without affecting the rise in short-circuit current induced by mucosal glucose or serosal prostaglandin E2. Mepacrine also inhibited the response to histamine, but not that to prostaglandin E2. 6. It is concluded that histamine induces intestinal secretion by stimulating the production of prostaglandins which then activate the secretory process.