Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells
Flavahan, N.A.
American Journal of Physiology 264(3 Pt 2): H722-H727
1993
ISSN/ISBN: 0002-9513 PMID: 8456975 Document Number: 417241
Certain endothelial receptors are coupled to a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory (G-i) protein. In pigs, hypercholesterolemia causes a selective impairment of this G-i protein-dependent pathway. Recent studies have suggested that hypercholesterolemia-induced endothelial dysfunction may be caused by lysophosphatidylcholine (LPC) derived from oxidized low-density lipoprotein (LDL). The aim of the present study was to determine whether LPC could inhibit the G-i protein-dependent pathway. Isolated rings of porcine coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution (37 degree C, 95% O-2-5% CO-2). In rings with endothelium contracted with prostaglandin F-2alpha, pertussis toxin (100 ng/ml) or LPC (10-5 M) inhibited the endothelium-dependent relaxations evoked by UK-14,304, an alpha-2-adrenergic agonist, or by serotonin, but not those caused by bradykinin or ADP. LPC also did not inhibit relaxations produced by SIN 1, an endothelium-derived relaxing factor-nitric oxide donor. After treatment of the rings with pertussis toxin, LPC no longer inhibited the endothelium-dependent relaxations to serotonin. Although LPC inhibited the responses of membrane-bound receptors that activate the pertussis toxin-sensitive G-i protein, LPC did not affect the endothelium-dependent relaxations evoked by direct activation of the pertussis toxin-sensitive G-i protein by fluoride. These results suggest that LPC selectively inhibits a G-i protein-dependent pathway in porcine endothelial cells possibly by disrupting receptor-G protein interactions. LPC that is associated with oxidized LDL may mediate in part the dysfunction in the endothelial G-i protein-dependent pathway associated with hypercholesterolemia.