Endothelin stimulates degradation of phospholipids in isolated rat hearts.
The abilities of endothelin-1 to cause cellular injury and to enhance the levels of inositol-1,4,5-triphosphate and the breakdown of [14C]arachidonate-labeled phospholipids have been examined in the isolated rat heart model. In 10 minutes, endothelin at 1 and 3 nM concentrations significantly increased the myocardial release of creatine kinase, suggesting endothelin-induced cell injury. The enhanced levels of myocardial inositol-1,4,5-triphosphate and diacyl glycerol by endothelin also suggest the increased breakdown of phosphatidylinositol-4,5-bisphosphate. In addition, endothelin also increased the degradation of other membrane phospholipids as observed by (1) a decrease in [14C]arachidonate radiolabel in phospholipids, (2) an increase in [14C]radiolabel in non-esterified fatty acids and triacyl glycerol, and (3) increased levels of non-esterified fatty acids. The potential role of endothelin-1 in myocardial ischemia-reperfusion injury is discussed.
Prasad
M R
MR
Department of Surgery, University of Connecticut Health Center, Farmington 06030.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D004075:Diglycerides; D016232:Endothelins; D005230:Fatty Acids, Nonesterified; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D015544:Inositol 1,4,5-Trisphosphate; D003402:Creatine Kinase