THE EFFECTS OF PURINE COMPOUNDS ON THE ISOLATED AORTA OF THE FROG RANA-TEMPORARIA

1 In the isolated aorta of the frog, Rana temporaria, adenosine concen tration-dependently, endothelium-independently relaxed adrenaline pre- constricted vessels. None of the adenosine analogues including D-5'-(N -ethylcarboxamide) adenosine (NECA), R- and S-N-6-(2-phenylisopropyl) adenosine (R-and S-PIA) and 2-chloroadenosine (2-CA), or the more sele ctive A(1), A(2) and A(3) agonists cyclopentyladenosine (CPA), CGS 216 80 and N-6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide (IB-MECA) r espectively, had any effect. 2 The non-selective adenosine antagonist, 8-p-sulphophenyl-theophylline (8-pSPT; 30 mu M) failed to inhibit ade nosine relaxations, as did N-G-nitro-L-arginine methyl ester (L-NAME; 0.1 mM) and indomethacin (30 mu M). 3 Adenosine 5'-triphosphate (ATP), alpha,beta-methylene ATP (alpha,beta-MeATP), beta,gamma-methylene ATP (beta,gamma-MeATP), 2-methylthio ATP (2-MeSATP) and uridine 5'-tripho sphate (UTP) all concentration-dependently contracted the frog aorta. ATP and alpha,beta-MeATP were equipotent and more potent than UTP and beta,gamma-MeATP; 2-MeSATP had little activity. 4 The P-2-purinoceptor antagonist, suramin (0.1 mM) inhibited contractions to alpha,beta-MeA TP but not to ATP. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic ac id (PPADS; 30 mu M) also inhibited contractions to alpha,beta-MeATP bu t not to ATP. Contractions to ATP were, however, inhibited by indometh acin (30 mu M). 5 In conclusion, in the frog aorta there appears to be a novel subclass of P-1-purinoceptor mediating vasodilatation, althou gh like the A(3) subclass it is not blocked by methylxanthines; a P-2- purinoceptor mediates vasoconstriction which resembles a P-2X subtype, based on the agonist potency of alpha,beta-MeATP being more potent th an 2-MeSATP (UTP has moderate activity) and PPADS is an effective anta gonist. There is no evidence for the presence of a P-2Y-purinoceptor, mediating vasodilatation, in this preparation.