G-proteins and endothelial responses.
G-proteins are transducing proteins that couple a large number of membrane-bound receptors to a variety of intracellular effector systems. Pertussis toxin ADP-ribosylates certain G-proteins causing inhibition of their function. In porcine coronary arteries, pertussis toxin inhibited the endothelium-dependent relaxations evoked by alpha-2-adrenergic or serotonergic receptor stimulation, and by aggregating platelets or thrombin. Relaxations to nitric oxide and endothelium-dependent relaxations to bradykinin, adenosine diphosphate or A23187 were unaffected by the toxin. Therefore, certain endothelium-dependent relaxations are mediated by activation of a pertussis toxin-sensitive G-protein in the endothelial cells, most likely Gi-protein. In porcine coronary arteries with regenerated endothelium (following in vivo denudation), the endothelium-dependent relaxations caused by the pertussis toxin-sensitive stimuli were reduced and were not further affected by pertussis toxin. Relaxations to the other stimuli were not altered by the regeneration process and were still not affected by the toxin. In regenerating endothelial cells there may be a selective impairment of the G-protein-dependent mechanism for releasing EDRF, which may predispose the blood vessel to vasospasm or the initiation of vascular disease.
Flavahan
N A
NA
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.
Vanhoutte
P M
PM
D000818:Animals; D002318:Cardiovascular Diseases / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D037342:Pertussis Toxin; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D009569:Nitric Oxide; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins