Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion.
Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial cells was more dependent on the extent of ATP depletion than on the inhibition of fatty acid oxidation. In addition, these studies were designed to determine if arachidonic acid release only occurred when ATP was depleted beyond a critical threshold level. To examine the relationship between arachidonic acid release and ATP depletion, cultured myocardial cells from neonatal rat hearts were labeled with [3H]arachidonate and [14C]palmitate. In response to ATP depletion with various metabolic inhibitors, [3H]arachidonic acid and [14C]palmitic acid were released from phospholipids. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidic acid were the major esterified sources of the arachidonate. The release of both fatty acids was related to the extent of ATP depletion and not whether a glycolytic or respiratory inhibitor was utilized. Various combinations and doses of metabolic inhibitors were used, and experimental conditions that produced a greater than 75% decrease in ATP content were associated with the accumulation of arachidonic acid. These results suggest that an ATP-dependent step may be linked to the accumulation of arachidonic acid during myocardial ATP depletion. It is suggested that myocardial cells may release arachidonic acid directly in response to ATP depletion.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D009840:Oligomycins; D010169:Palmitic Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D016718:Arachidonic Acid; D019308:Palmitic Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose