Abstract
Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive G(i-2) protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: G(i-2) protein-independent), serotonin (5-HT: G(i-2) protein- dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive G(iα-2) between control and lysoPC-treated cells. Activation of the G(i-2) protein by serotonergic or α2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of G(iα-2) protein in membranes from control but not lysoPC-treated cells. However, direct activation of the G(i-2) protein by mastoparan inhibited the ADP- ribosylation in membranes from control and lysoPC-treated cells. The toxin- catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTPγS binding to the G(i-2) protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:G(i-2)-protein uncoupling.
Original language | English (US) |
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Pages (from-to) | 345-352 |
Number of pages | 8 |
Journal | Journal of cardiovascular pharmacology |
Volume | 28 |
Issue number | 3 |
DOIs | |
State | Published - 1996 |
Keywords
- Endothelial dysfunction
- Hypercholesterolemia
- Modified lipoproteins
- Nitric oxide
- Superoxide anion
- Western blot
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine