Evidence for an inhibitory prejunctional P1-purinoceptor in the rat portal vein with characteristics of the A2 rather than of the A1 subtype.

The effects of adenosine (ADO) and of the adenosine analogues 5'-N-ethylcarboxamideadenosine (NECA), 2-chloroadenosine (2-CADO), L- and D-phenylisopropyladenosine (L- and D-PIA) and N6-cyclohexyladenosine (CHA) were compared on the contractile response of the isolated rat portal vein to perivascular adrenergic nerve stimulation. The order of potency at 20% inhibition of control values was NECA greater than or equal to 2-CADO = L-PIA greater than D-PIA = CHA greater than ADO. At this level of inhibition only D-PIA had a significant inhibitory effect against a matched concentration of exogenous NA. The difference in potency between L-PIA and D-PIA was approximately 3-fold. 8-Phenyltheophylline, a potent P1-purinoceptor antagonist, had a direct inhibitory effect on the tissue per se and therefore could not be used to antagonise these compounds. It is concluded that NECA, 2-CADO, L-PIA, D-PIA, CHA and ADO mediate their inhibitory effect in the rat portal vein via a prejunctional P1-purinoceptor which displays characteristics of the A2 classification, in contrast to that found to date in other adrenergic and cholinergic nerve terminals where it displays characteristics of the A1 classification.