Role of the vasopressin V(1) receptor in regulating the epithelial functions of the guinea pig distal colon

Abstract

Vasopressin has a wide spectrum of biological action. In this study, the role of vasopressin in regulating electrolyte transport in the colon was elucidated by measuring the short-circuit current (I(sc)) as well as the Na(+), K(+), and Cl(-) flux in a chamber-mounted mucosal sheet. The cytosolic Ca(2+) concentration ([Ca(2+)](i)) was also measured in fura 2-loaded cells by fluorescence imaging. Serosal vasopressin decreased I(sc) at 10(-9) M and increased I(sc) at 10(-7)-10(-6) M. The decrease in I(sc) was accompanied by two effects: one was a decrease in the amiloride-sensitive Na(+) absorption, whereas the other was an increase in the bumetanide-sensitive K(+) secretion. The increase in I(sc) was accompanied by an increase in the Cl(-) secretion that can be inhibited by serosal bumetanide or mucosal diphenylamine-2-carboxylate. Vasopressin caused an increase in [Ca(2+)](i) in crypt cells. These responses of I(sc) and the [Ca(2+)](i) increase in crypt cells were all more potently inhibited by the vasopressin V(1) receptor antagonist than by the V(2) receptor antagonist. These results suggest that vasopressin inhibits electrogenic Na(+) absorption and stimulates electrogenic K(+) and Cl(-) secretion. In all of these responses, the V(1) receptor is involved, and the [Ca(2+)](i) increase may play an important role.