title: Antagonism of coronary artery relaxation by adenosine A2A-receptor antagonist ZM241385.
abstract: We have tested the existence of functional A2A adenosine receptor in porcine coronary artery using, for the first time, the new A2A antagonist ZM241385. Nonselective agonist NECA and A2A-selective agonist CGS21680 produced concentration-dependent relaxation of prostaglandin F2alpha (PGF2alpha)-precontracted endothelium intact (E+) and denuded (E-) rings. Relaxation was significantly greater in E+ rings than in E-rings. A2A adenosine receptor-selective antagonist, ZM241385 (10(-6) M), significantly attenuated the relaxation responses. The antagonism of ZM241385 was compared with that of SCH58261 (10(-6)M), another A2A adenosine receptor-selective antagonist, which also significantly attenuated the relaxation response to both agonists. However, ZM241385 produced a significantly greater shift of the relaxation-response curves to the right compared with SCH58261 both in E+ and E- rings. The data show for the first time that ZM241385 is a potent A2A-receptor antagonist in porcine coronary artery and a useful tool to study A2A-receptor function.
authors.affiliation: Department of Pharmacology, ECU School of Medicine, Greenville, North Carolina 27858, USA.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Arif Hasan
authors.forename: W
authors.initials: W
authors.lastname: Abebe
authors.forename: S J
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000145:classification; D013552:Swine; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000959:Antihypertensive Agents; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D015237:Dinoprost; D000241:Adenosine