Guanine Nucleotides Stimulate Arachidonic Acid Release by Phospholipase A2 in Saponin-Permeabilized Human Platelets1

Abstract

GTP or GTPγS alone caused low but significant liberation of arachidonic acid in saponin-permeabilized human platelets but not in intact platelets. GTP or GTPγS also enhanced thrombin-induced [ ³ H]arachidonic acid release in permeabilized platelets. Inhibitors of the phospholipase C (neomycin)/diacylglycerol lipase (RHC 80267) pathway for arachidonate liberation did not reduce the [ ³ H]arachidonic acid release. The loss of [ ³ H]arachidonate radioactivity from phosphatidylcholine was almost equivalent to the increase in released [ ³ H]arachidonic acid, suggesting the hydrolysis of phosphatidylcholine by phospholipase A ₂ . The effect of GTPγS was greater at lower Ca ²⁺ concentrations. These data indicate that the release of arachidonic acid by phospholipase A ₂ in saponin-treated platelets may be linked to a GTP-binding protein.