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

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 [³H] arachidonic acid release in permeabilized platelets. Inhibitors of the phospholipase C (neomycin)/diacylglycerol lipase (RHC 80267) pathway for arachidonate liberation did not reduce the [³H] arachidonic acid release. The loss of [³H]arachidonate radioactivity from phosphatidylcholine was almost equivalent to the increase in released [³H] arachidonic acid, suggesting the hydrolysis of phosphatidylcholine by phospholipase A₂. The effect of GTPγS was greater at lower Ca²⁺ concentrations. These data indicate that the release of arachidonic acid by phospholipase A₂ in saponin-treated platelets may be linked to a GTP-biding protein.