Effects of ATP on phosphatidylinositol-phospholipase C and inositol 1-phosphate accumulation in rat brain synaptosomes.
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]arachidonoyl-phosphatidylinositol which was introduced into saponin-permeabilized synaptosomes, ATP (1 mM) and free Ca2+ (approximately 20 microM) enhanced the phospholipase C hydrolysis of this substrate to form labeled diacylglycerol. When the same permeabilized synaptosomal preparation was incubated with [2-3H]inositol-phosphatidylinositol, 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 1-phosphate to inositol could not be overcome by increasing the Mg2+ concentration 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.
Huang
H M
HM
Biochemistry Department, University of Missouri, Columbia 65203.
Sun
G Y
GY
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008246:Lysophospholipids / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013403:Sugar Phosphates / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D007295:Inositol Phosphates; D008246:Lysophospholipids; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; C025296:arachidonyl phosphatidylinositol; C002647:inositol 1-phosphate; D007294:Inositol; D000255:Adenosine Triphosphate; D008094:Lithium; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D018021:Lithium Chloride; D002118:Calcium