Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver

Abstract

Changes in perfusate Ca2+ (measured with a Ca(2+)-selective electrode) and changes in bile calcium (measured by atomic absorption spectroscopy) were continuously and simultaneously monitored after infusion of (a) vasopressin, (b) glucagon and (c) both vasopressin and glucagon together to the perfused rat liver. Also monitored were perfusate glucose and oxygen concentrations and bile flow. Vasopressin induces a sharp, transient, pulse of increased bile flow and increased bile calcium within 1 min of infusion, concomitant with rapid changes in perfusate Ca2+ fluxes, glucose output and oxygen uptake. This is immediately followed by a decrease in both bile flow and bile calcium for as long as the hormone is administered. Changes induced by glucagon are a relatively slow onset of perfusate Ca2+ efflux and oxygen uptake, but rapid glucose output, and a small but significant and transient decrease in bile flow and bile calcium which, despite the continued infusion of the hormone, spontaneously and rapidly returns to normality. However, the greatest responses are observed after co-administration of both hormones. Coincident with the augmented perfusate Ca2+ fluxes (influx) seen in earlier work, there occurs within 1 min of vasopressin infusion a sharp increase in bile secretion and bile calcium greater in magnitude than that produced by vasopressin alone. Immediately thereafter bile secretion and bile calcium decline below basal values and remain there for as long as the hormones are administered. Glucagon and vasopressin therefore each have opposing effects on bile flow and bile calcium. However, the action of vasopressin is enhanced by the prior administration of glucagon. The data thus reveal features about the actions of glucagon and Ca(2+)-mobilizing hormones on bile flow and bile calcium not previously recorded and provide a novel framework around which the whole issue of hepato-biliary Ca2+ homoeostasis can be assessed in normal and diseased liver.