title: Relative agonist potencies of C2-substituted analogues of adenosine: evidence for adenosine A2B receptors in the guinea pig aorta.
abstract: Nine C2-substituted adenosine analogues that are potent and selective for the A2-adenosine receptor were tested for their ability to induce relaxations of the guinea pig aorta. Compounds tested were 2-phenylethoxyadenosine (PEA), 2-phenylethoxy-5'-N-ethylcarboxamidoadenosine (PENECA), 2-cyclohexylethoxyadenosine (CEA), 2-fluorophenylethoxyadenosine (FPEA), 2-methoxyphenylethoxyadenosine (MPEA), 2-naphthylethoxyadenosine (NEA), 2-phenylaminoadenosine (CV-1808), 2-phenylethylaminoadenosine (PEAA) and 2-carboxyethylphenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680). The responses to these agents were compared to those of three standard adenosine receptor agonists, 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA) and R-N6-phenylisopropyladenosine (R-PIA). The C2-ethoxyadenosine analogues were 30- to 140-fold less potent than NECA and the C2-amino-substituted analogues were 250 to 1000-fold less potent than NECA at inducing relaxations of the guinea pig aorta. All of the analogues were also less potent than the A1-selective agonist R-PIA. However, only responses to NECA were competitively antagonized by the non-selective adenosine receptor antagonist 8-phenyltheophylline (8-PT), pKB = 6.83 +/- 0.05. The results suggest that the C2-substituted analogues produce relaxations of the guinea pig aorta through a combination of actions at A2-adenosine receptors and at xanthine resistant sites. The lack of potency of these analogues at activating the xanthine sensitive A2-receptors in the guinea pig aorta suggests that these adenosine receptors may be of the A2b-subtype.
authors.affiliation: Department of Pharmacology, Whitby Research, Inc., Richmond, VA 23220.
authors.forename: P L
authors.initials: PL
authors.lastname: Martin
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000145:classification / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010627:Phenethylamines; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine