Lysophosphatidylcholine causes cGMP-dependent verapamil-sensitive Ca2+ influx in vascular smooth muscle cells.
Lysophosphatidylcholine (lyso-PC) is a vasoactive phospholipid present in oxidized low-density lipoprotein. We used a coculture model of the vascular wall to study its interaction with endothelial cells (EC) and vascular smooth muscle cells (SMC). Lyso-PC was taken up readily by SMC and gradually acylated to phosphatidylcholine. Low concentrations (< or = 1 microM) of lyso-PC present in the interstitial medium of an EC-SMC coculture system were taken up primarily by the SMC. Lyso-PC produced a rapid two- to three-fold increase in SMC guanosine 3',5'-cyclic monophosphate (cGMP) levels, reaching a maximum in 1 min. This increase was associated with decreased SMC proliferation and increased calcium influx. The increase in intracellular calcium was inhibited by verapamil and KT5823, a specific cGMP-dependent kinase inhibitor, while a similar increase was produced by the membrane-permeant cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate. These studies suggest that SMC are the primary target for the biological effects of lyso-PC present in the vessel wall and that the responses are mediated by calcium influx, possibly due to opening of a verapamil-sensitive cGMP kinase-dependent channel.
Department of Anesthesia, University of Iowa, Iowa City 52242.
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D016257:Fura-2; D007211:Indoles; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D013050:Spectrometry, Fluorescence; D013552:Swine; D014700:Verapamil / Q000494:pharmacology*
D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; D008244:Lysophosphatidylcholines; D047428:Protein Kinase Inhibitors; C073601:KT 5823; C016276:8-bromocyclic GMP; D014700:Verapamil; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2