A model to study physiological activation of phospholipase A2 and vasorelaxation by lysophosphatidylcholine.
Earlier we demonstrated that micellar solutions of LPC caused endothelium-dependent relaxation of rabbit thoracic aorta and bovine intrapulmonary artery and vein through a cyclic GMP-dependent mechanism. The availability of LPC for vasorelaxation depends on its production by deacylation of PC by PLA2. We assessed the possible activation of PLA2 by commonly used vasorelaxants such as acetylcholine, bradykinin, calcium ionophore A23187 and thrombin and vasoconstrictors like histamine and phenylephrine in the presence of indomethacin in a model system where 14C PC was incorporated into bovine intrapulmonary arterial segments. Taking the ratio of 14C PC:LPC formed by exogenous PLA2 as an index of deacylation, we found that while all the agents relaxed the strips in an endothelium-dependent manner, only thrombin caused relaxation followed by an increase in 14C LPC and a concomittant decrease in 14C PC indicating activation of PLA2. Our data show that PC/PLA2 system can be activated to generate LPC for vascular relaxation under specific physiological conditions. This model system can be used to monitor PLA2 activity and LPC production to compensate flow and pressure induced changes in arteries.
Menon
N K
NK
Huntington Medical Research Institutes, Department of Experimental Cardiology Pasadena, CA 91105.
Pataricza
J
J
Zehetgruber
M
M
Bing
R J
RJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002417:Cattle; D004727:Endothelium / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D050356:Lipid Metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology
D002250:Carbon Radioisotopes; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010656:Phenylephrine; D000001:Calcimycin; D006632:Histamine; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin