Adenosine receptor-mediated coronary artery relaxation and cyclic nucleotide production.
We investigated the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in adenosine (ADO) receptor-mediated coronary artery relaxation. Rings from left anterior descending coronary artery, with the endothelium mechanically removed, contracted with prostaglandin F2 alpha and relaxed in a concentration-dependent manner to ADO, 2-chloroadenosine (CAD), l-N6-(2-phenylisopropyl)adenosine (R-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA). These relaxations were blocked by addition of the ADO receptor antagonist 8-(sulfophenyl)theophylline (8-SPT), indicating ADO receptor involvement. In an endothelium-free membrane preparation, ADO, CAD, and R-PIA all stimulated adenylate cyclase activity in a concentration-dependent manner, and these responses were blocked by 8-SPT. The increase in adenylate cyclase activity produced by ADO, CAD, and R-PIA was completely dependent on the presence of guanosine 5'-triphosphate, suggesting G protein involvement. Surprisingly, NECA and CGS-21680 did not increase adenylate cyclase activity. Unlike atrial natriuretic factor, neither NECA, CAD, R-PIA, nor ADO increased guanylate cyclase activity, suggesting that cGMP is not involved in ADO receptor-mediated relaxation. Data presented in this study support the hypothesis that ADO receptor-mediated coronary artery relaxation may involve cAMP; however, the inability of NECA and CGS-21680 to stimulate adenylate cyclase suggests that the ADO receptor-signaling mechanisms in coronary artery may be more complicated than agonist interaction with a single adenylate cyclase-coupled A2 adenosine receptor.
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
D J
DJ
Cushing
G L
GL
Brown
M H
MH
Sabouni
S J
SJ
Mustafa
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000096:biosynthesis*; D006160:Guanosine Triphosphate / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D011983:Receptors, Purinergic / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
D011983:Receptors, Purinergic; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000241:Adenosine