Stimulation by vasopressin and alpha-catecholamines of phosphatidylinositol formation in isolated rat liver parenchymal cells

The effects of glucagon, epinephrine, and vasopressin on phospholipid synthesis and glycogen phosphorylase a activity were investigated in rat hepatocytes. There was a stimulation of [32P]Pi ncorporation into phosphatidylinositol by vasopressin and epinephrine but not by glucagon. A mild degree of calcium depletion abolished the activation of glycogen phosphorylase by vasopressin but the increase in [32P]Pi ncorporation into phosphatidylinositol was still present. However, the activation of glycogen phosphorylase by epinephrine was not abolished by any degree of calcium depletion. The increase in [32P]Pi ncorporation into phosphatidylinositol due to epinephrine was mediated through an amechanism which was very sensitive to inhibition by prazosin, inhibited by phentolamine and yohimbine at fairly high concentrations, and unaffected by propranolol. The uptake of [2-3H]inositol into phosphatidylinositol was accelerated by hormones and correlated poorly with 32P uptake into this phospholipid. Depletion of calcium from or the addition of manganese to the incubation medium markedly enhanced the uptake of labeled inositol into phosphatidylinositol. However, these increases in [2-3H]inositol incorporation did not parallel any changes in basal or hormone stimulated 32P incorporation into phosphatidylinositol. The use of labeled inositol to measure phosphatidylinositol synthesis is unreliable since it appears to reflect the activity of the freely reversible Mn2+-dependent enzyme which catalyzes the reaction of CDP-diacylglycerol with inositol to give cytidine monophosphate and phosphatidylinositol. These data support the hypothesis that vasopressin and catecholamine activation of phosphatidylinositol turnover in hepatocytes is linked in an unknown fashion to the release of bound intracellular calcium and the entry of extracellular calcium.