GLYCOGENOLYTIC EFFECTS OF THE CALCIUM IONOPHORE A23187, BUT NOT VASOPRESSIN OR ANGIOTENSIN, IN FERTALRAT HEPATOCYTES

Abstract

Vasopressin, angiotensin II and phenylephrine stimulate glycogenolysis in postnatal rat liver by a non-cAMP, calcium-mediated mechanism. To determine whether these hormones also promote glycogenolysis in fetal liver, we have examined their effects, and those of the calcium ionophore A23187 (A), on glycogen metabolism in cultured fetal rat hepatocytes. Vasopressin and angiotensin (10−10-10−7M) had no effects on either 14C-glucose incorporation into glycogen or phosphorylase a activity. However, A at concentrations of 1 and 10 uM inhibited glycogen synthesis by 31.3 and 89.1 percent, respectively (p< 0.001) and stimulated phosphorylase a activity by 66.9 and 184.1 percent respectively (p < 0.01). Incubation of cells in calcium-deficient medium markedly attenuated the effects of A on glycogen synthesis. As in postnatal liver, glucagon (1 and 20 nM) and isoproterenol (1 and 10 uM), which activate adenylate cyclase, inhibited glycogen synthesis and stimulated phosphorylase a activity in fetal hepatocytes. The minimal effective concentration of phenylephrine was 10 times that of isoproterenol. These results indicate striking differences in the ontogeny of cAMP-mediated and non-cAMP, calcium-mediated processes which regulate hepatic glycogenolysis. Since increases in cytosolic calcium induce glycogenolysis in fetal rat liver, the weak or absent responses to vasopressin, angiotensin and α - adrenergic agonists may result from defects in hormone-receptor binding or in postreceptor events leading to the mobilization of intracellular calcium stores. NIH grants HD07447 and HDO6301.