Antagonism of coronary artery relaxation by adenosine A2A-receptor antagonist ZM241385.
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.
Arif Hasan
A Z
AZ
Department of Pharmacology, ECU School of Medicine, Greenville, North Carolina 27858, USA.
Abebe
W
W
Mustafa
S J
SJ
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
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