Guanosine 5'-O-(3-thiotriphosphate) causes endothelium-dependent, pertussis toxin-sensitive relaxations in porcine coronary arteries.
To determine whether direct stimulation of endothelial G-proteins causes relaxations of the underlying vascular smooth muscle, the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and sodium fluoride were studied in porcine coronary arteries and endothelial cells. Isometric tension was measured in coronary rings contracted with prostaglandin F2 alpha. GTP gamma S (in the presence of saponin) and sodium fluoride (in the presence of AlCl3) relaxed rings with, but not those without endothelium. The responses were inhibited by nitro-L-arginine and pertussis toxin. In membrane fractions of coronary endothelial cells, GTP gamma S and sodium fluoride inhibited the ADP-ribosylation of G-proteins catalyzed with [32P]-NAD and pertussis toxin. These data suggest that direct stimulation of G-proteins in endothelial cells by GTP gamma S and sodium fluoride causes a pertussis toxin-sensitive relaxation which may be attributed to the release of nitric oxide.
Shibano
T
T
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
Codina
J
J
Birnbaumer
L
L
Vanhoutte
P M
PM
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine; D037342:Pertussis Toxin; D012503:Saponins / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D012503:Saponins; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D019335:Nitroarginine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012969:Sodium Fluoride; D001120:Arginine; D015237:Dinoprost; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins