title: G proteins and endothelium-dependent relaxations.
abstract: Endothelial cells control the tone of the underlying smooth muscle by releasing relaxing factors (nitric oxide, NO, prostacyclin and endothelium-derived hyperpolarizing factor). G proteins couple a number of endothelial cell receptors to the activation of NO synthase. Pertussis toxin selectively ADP-ribosylates certain G proteins (mainly G(i)). In the porcine coronary artery, pertussis toxin inhibits the release of NO evoked by certain (serotonin, alpha2-adrenergic agonists, leukotrienes, thrombin), but not all, (bradykinin, adenosine diphosphate) endothelium-dependent vasodilators. This suggests that both G(i) and G(q) proteins can couple receptor activation to the increase in endothelial Ca2+ concentration required to stimulate NO synthase. In arteries with regenerated endothelium and in cultured endothelial cells, the release of NO evoked by pertussis-toxin-sensitive mechanisms is severely reduced or absent, while the response to other endothelium-dependent agonists is normal. To judge from experiments with cultured endothelial cells, the curtailment in pertussis-toxin-sensitive release of NO is due to an abnormal function rather than a reduced presence of G(i) proteins, or a reduced sensitivity of the cell membrane receptor. The selective impairment of G(i) proteins in regenerated endothelial cells predisposes the blood vessel wall to vasospasm and to the initiation of the atherosclerotic process.
authors.affiliation: INSERM, Hôpital Lariboisière, Paris, France. cboulang@infobiogen.fr
authors.forename: C M
authors.initials: CM
authors.lastname: Boulanger
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D019204:GTP-Binding Proteins