Identification and functional characterization of A1 and A2 adenosine receptors in the rat vas deferens: a comparison with A1 receptors in guinea pig left atrium and A2 receptors in guinea pig aorta.
This study was undertaken to characterize the adenosine receptors in the rat vas deferens. Because adenosine receptors have been well characterized in the cardiovascular system of the guinea pig, antagonist dissociation constants (pKB values) in the rat vas deferens were compared with those from the left atrium (A1) and the aorta (A2) of the guinea pig. The A1-selective agonists (+/-)-N6-endonorbornan-2-yl-5'-N-hydroxy ethylcarboxamidoadenosine (N-0723) and N6-cyclohexyladenosine (CHA) and the nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) inhibited the electrically evoked contractions of both the vas deferens and left atrium with a potency order of N-0723 > NECA = CHA. The A2a-selective agonist 2-[p-(2-carboxyethyl)-phenethylamino]5'-N-ethylcarboxamidoadenosin e (CGS21680) was equipotent to NECA in the vas deferens but was 500-fold less potent than NECA in the left atrium. In the aorta only NECA was a potent agonist. The nonselective adenosine receptor antagonist 8-phenyltheophylline antagonized the responses in all three tissues with approximately equal potency (pKB approximately 6.6). In the rat vas deferens, the A1-selective antagonists (+/-)-N6-endonorboman-2-yl-9-methyladenine (N-0861) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) were more potent at antagonizing the responses to A1-selective agonists (pKB approximately 8.8 and 6.4, respectively) than they were at antagonizing the responses to NECA and CGS21680 (pKB = 6.3 and < 5, respectively). However, in the left atrium, N-0861 (pKB = 6.2) and DPCPX (pKB = 8.9) were no more potent in antagonizing responses to the A1-selective agonists than they were in antagonizing responses to NECA.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
P L
PL
Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.
May
J M
JM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009636:Norbornanes / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D009636:Norbornanes; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C073387:N 0861; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D000225:Adenine; D000241:Adenosine