PHOSPHATIDYLINOSITOL METABOLISM IN RAT HEPATOCYTES STIMULATED BY GLYCOGENOLYTIC HORMONES - EFFECTS OF ANGIOTENSIN, VASOPRESSIN, ADRENALINE, IONOPHORE-A23187 AND CALCIUM-ION DEPRIVATION

The effects on phosphatidylinositol metabolism of 3 Ca2+-mobilizing glycogenolytic hormones, namely angiotensin [A], vasopressin [VP] and adrenaline [epinephrine, EPI], were investigated. All 3 hormones stimulate both phosphatidylinositol breakdown and the labeling of this lipid with 32P. The response to A occurs quickly, requires a high concentration of the hormone and is prevented by [1-Sar, 8-Ile]A, a specific A antagonist that does not prevent the responses to VP and to EPI. This response seems to be mediated by A-specific receptors. [1-Deaminocysteine,2-phenylalanine,7-(3,4-didehydroproline),8-arginine]VP, a VP analog with enhanced antidiuretic potency, is relatively ineffective at stimulating phosphatidylinositol metabolism. The hepatic VP receptors that stimulate phosphatidylinositol breakdown may be different in their ligand selectivity from the antidiuretic vasopressin receptors that activate renal adenylate cyclase. Incubation of hepatocytes with ionophore A23187 [2-[(3.beta.,9.alpha.,11.beta.-trimethyl)-8-(2-pyrrole carboxymethyl)-1,7-dioxaspiro [6.6] undecyl-2.beta.-methyl]-5-methyl aminobenzoxazole-4-carboxylic acid], a bivalent-cation ionophore, neither mimicked nor appreciably changed the effects of VP on phosphatidylinositol metabolism, suggesting that phosphatidylinositol breakdown is not controlled by changes in the cytosol Ca2+ concentration. Hormonal stimulation of phosphatidylinositol breakdown and resynthesis persists in cells incubated for a substantial period in EGTA [ethyleneglycol bis (.beta.-aminoethyl ether) N,N''-tetraacetic acid], although this treatment somewhat decreased the phosphatidylinositol response of the hepatocyte. The phosphatidylinositol response of the hepatocyte therefore appears not to be controlled by changes in cytosol Ca2+ concentration, despite the fact that this ion is thought to be the 2nd messenger by which the same hormones control glycogenolysis. Phosphatidylinositol breakdown is apparently an integral reaction in the stimulus-response coupling sequence(s) that link(s) activation of .alpha.-adrenergic, VP and A receptors to mobilization of Ca2+ in the rat hepatocyte.