LYSOPHOSPHATIDYLCHOLINE CAUSES CGMP-DEPENDENT VERAPAMIL-SENSITIVE CA2+ INFLUX IN VASCULAR SMOOTH-MUSCLE CELLS

被引:33
作者
STOLL, LL [1 ]
SPECTOR, AA [1 ]
机构
[1] UNIV IOWA, DEPT BIOCHEM, IOWA CITY, IA 52242 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 264卷 / 04期
关键词
VASORELAXATION; COCULTURE; PROLIFERATION;
D O I
10.1152/ajpcell.1993.264.4.C885
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 (less-than-or-equal-to 1 muM) 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.
引用
收藏
页码:C885 / C893
页数:9
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