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 concentration‐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 selective A 1 , A 2 and A 3 agonists cyclopentyladenosine (CPA), CGS 21680 and N 6 ‐(3‐iodobenzyl) adenosine‐5′‐ N ‐methylcarboxamide (IB‐MECA) respectively, had any effect. 2 The non‐selective adenosine antagonist, 8‐ p ‐sulphophenyl‐theophylline (8‐ p SPT; 30 μ m ) failed to inhibit adenosine relaxations, as did N G ‐nitro‐L‐arginine methyl ester (L‐NAME; 0.1 mM) and indomethacin (30 μ m ). 3 Adenosine 5′‐triphosphate (ATP), α,β‐methylene ATP (α,β‐MeATP), β,γ‐methylene ATP MeATP), 2‐methylthio ATP (2‐MeSATP) and uridine 5′‐triphosphate (UTP) all concentration‐dependently contracted the frog aorta. ATP and α,β‐MeATP were equipotent and more potent than UTP and β,γ‐MeATP; 2‐MeSATP had little activity. 4 The P 2 ‐purinoceptor antagonist, suramin (0.1 mM) inhibited contractions to α,β‐MeATP but not to ATP. Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS; 30 μ m ) also inhibited contractions to α,β‐MeATP but not to ATP. Contractions to ATP were, however, inhibited by indomethacin (30 μ m ). 5 In conclusion, in the frog aorta there appears to be a novel subclass of P 1 ‐purinoceptor mediating vasodilatation, although 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 α,β‐MeATP being more potent than 2‐MeSATP (UTP has moderate activity) and PPADS is an effective antagonist. There is no evidence for the presence of a P 2Y ‐purinoceptor, mediating vasodilatation, in this preparation.