Effects of ATP on Phosphatidylinositol‐Phospholipase C and Inositol 1‐Phosphate Accumulation in Rat Brain Synaptosomes

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Abstract
Incubation of rat brain synaptosomes prelabeled with [2-3H]inositol resulted in a time-dependent release of labeled inositol 1-phosphate. This process was Ca2+-dependent, and ATP (1 mM) enhanced the inositol 1-phosphate formation three-to fivefold. Using [1-14C]arachidonyl-phosphatidylinositol which was introduced into saponin-permeabilitzed synaptosomes, ATP (1 mM) and free Ca2+ (.apprx. 20 .mu.M) enhanced the phospholipase C hydrolysis of this substrate to form labeled diacylglycerol. When the same permeabilized synaptosomal preparation was incubated with [2-13H]inositol-phosphatidylinossitol, ATP not only enhanced the formation of labeled inositol 1-phosphate, but also inhibited the conversion of inositol 1-phosphate to inositol. Furthermore, ATP appeared to reduce the Ca2+ requirement of the phosphatidylinositol-phospholipase C. Inhibition of the conversion of inositol l-phosphate to inositol could not be overcome by increasing the Mg2+ concentrations in the incubation medium. Although the ATP effect is not viewed as a receptor-mediated event, it is possible that such an event may occur in synaptosomes under conditions in which intrasynaptic Ca2+ concentration becomes elevated.