Regulation of a liver plasma membrane phosphoinositide phosphodiesterase by guanine nucleotides and calcium

Abstract

Rat liver plasma membranes are enriched in a Ca²⁺-dependent phosphodiesterase active on phosphatidylinositol 4,5-P₂ and phosphatidylinositol 4-P, but not phosphatidylinositol. Inositol-P₃ is the first product of the reaction, but is rapidly degraded. Micromolar concentrations of GTP and its nonhydrolyzable analogues stimulate the reaction, whereas GDP, GMP and other nucleoside triphosphates are inactive. GTP and its analogues decrease the requirement of the reaction for Ca²⁺ and also increase its activity at saturating Ca²⁺. These results support the hypothesis that guanine nucleotides and a guanine nucleotide binding regulatory protein are involved in coupling the receptors for Ca²⁺-mediated agonists to the breakdown of plasma membrane phosphatidylinositol 4,5-P₂.