title: Adenosine-5'-uronamides rapidly desensitize the adenosine A2 receptor in coronary artery.
abstract: This study examined the structure-activity-relationship (SAR) of adenosine analogs and their ability to induce tachyphylaxis in vascular smooth muscle. Adenosine-5'-uronamides,5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-cyclopropylcarboxamidoadenosine (CPCA), and 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680), evidenced rapid desensitization of the A2 vasorelaxant response in porcine coronary artery in vitro whereas adenosine, 2-chloroadenosine (CAD), or 2-[(2-cyclohexylethyl)-amino]adenosine (CGS 22492) failed to do so. Tissues with prior exposure to NECA exhibited mitigated relaxation responses to adenosine, CAD, and NECA but not to isoproterenol, forskolin, pinacidil, or sodium nitroprusside (SNP). The data suggest that adenosine-5'-uronamides homologously desensitize the A2 receptor in porcine coronary artery smooth muscle.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
authors.forename: S R
authors.initials: SR
authors.lastname: Makujina
authors.forename: S J
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine; D013618:Tachyphylaxis
chemical_list: D003510:Cyclohexanes; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C070485:2-((2-cyclohexylethyl)amino)adenosine; D015762:2-Chloroadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C024311:N-cyclopropyl adenosine-5'-carboxamide; D000241:Adenosine