Stimulation of phosphatidylinositol 4,5-bisphosphate hydrolysis in hepatocytes by vasopressin.
Hepatocyte phosphatidylinositol 4,5-bisphosphate (4,5-P2), phosphatidylinositol 4-phosphate (4-P), and phosphatidylinositol were labeled with 3H when rats were injected intraperitoneally with 200 microCi of [2-3H] myo-inositol 18 h previously. Phosphatidylinositol 4,5-P2 and phosphatidylinositol 4-P accounted for 0.84 +/- 0.06 and 7.48 +/- 0.36%, respectively, of the total [3H] myo-inositol containing phospholipids. The breakdown of phosphatidylinositol 4,5-P2 was stimulated transiently (maximum effect seen at 15 s) and in a Ca2+-dependent manner by 10(-8) M vasopressin. Phosphatidylinositol 4-P breakdown was enhanced to a smaller, but longer, extent by vasopressin, whereas no changes in phosphatidylinositol were detected up to 120 s. Subcellular fractionation studies also showed no preferential breakdown of phosphatidylinositol in plasma membranes at 5-20 min. Only doses of vasopressin (10(-8) and 10(-7) M) in excess of those producing maximum effects on phosphorylase activation and Ca2+ efflux (10(-9) M) were effective at stimulating phosphatidylinositol 4,5-P2 breakdown. It is concluded that phosphatidylinositol 4,5-P2 breakdown induced by vasopressin in rat hepatocytes is not responsible for the mobilization of Ca2+ which leads to the activation of phosphorylase. On the contrary, it is Ca2+-dependent and appears to require the occupation of more receptors than are required for Ca2+ mobilization and phosphorylase activation.
D000818:Animals; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D014667:Vasopressins; D007294:Inositol