title: Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium.
abstract: This study was designed to investigate the effects of a series of adenosine analogues on porcine coronary artery in vitro. In both endothelium-intact and -denuded rings, 5'-(N-ethylcarboxamido) adenosine (NECA), 2-[p-(2-carboxyethyl)]phenylethylamino-5'-N-ethylcarboxamidoadenos ine (CGS-21680), 2-chloroadenosine (CAD), N6-R-phenylisopropyladenosine (R-PIA), 2-phenylaminoadenosine (PAA), N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), and N6-S-phenylisopropyladenosine (S-PIA) produced concentration-dependent relaxations. The rank order of potency was consistent with A2-adenosine receptor identification. The xanthine adenosine antagonist, 8-(sulfophenyl) theophylline (8-SPT), attenuated the relaxant responses to all the agonists in the endothelium-intact rings and to only CAD, R-PIA, PAA, CHA, CPA, and S-PIA in the denuded preparations. Except for NECA and CGS-21680, the slopes of the relaxation curves and the dissociation constant (Kb) values for 8-SPT were similar for all agonists. In addition, endothelium removal selectively reduced the responses to NECA and CGS-21680. The adenosine receptor agonist, CGS-22988, also relaxed the denuded rings in a manner insensitive to blockade by 8-SPT. The data suggest that multiple A2-adenosine receptors exist on the smooth muscle and endothelium of porcine coronary artery, mediating relaxation. Whereas the smooth muscle contains both xanthine-sensitive and -insensitive A2-receptors, which can be activated by a wide range of adenosine agonists, the endothelium possesses xanthine-sensitive receptors that can be stimulated selectively by certain adenosine agonists, including 5'-uronamide derivatives, such as NECA and CGS-21680. The smooth muscle also appears to contain xanthine-insensitive A4-receptors activated by CGS-22988.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
authors.forename: W
authors.initials: W
authors.lastname: Abebe
authors.forename: S R
authors.initials: SR
authors.lastname: Makujina
authors.forename: S J
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D015237:Dinoprost; D000241:Adenosine