CHARACTERIZATION OF THE PREJUNCTIONAL ADENOSINE RECEPTORS IN THE RAT ANOCOCCYGEUS MUSCLE

Adenosine receptor agonists inhibited electrically-evoked contractions of the rat isolated anococcygeus muscle. ?The compounds tested were: N-6-cyclopentyladenosine (CPA), N((S,trans)-2-hydroxycyclopentyl)adeno sine (GR79236), the R- and S-isomers of phenylisopropyladenosine (PIA) , 5'-N-ethylcarboxamidoadenosine (NECA), (2-carboxyethyl)phenyl)ethyl) amino)-N-ethylcarbox- amidoadenosine (CGS 21680) and N-((2-methylpheny l)methyl) adenosine (metrifudil). The rank order of agonist potency wa s: CPA = R-PIA = GR79236 = NECA >> S-PIA > metrifudil > CGS 21680, whi ch is consistent with an effect mediated by adenosine A(1) receptors. A similar rank order of potency was obtained for inhibition of electri cally-evoked contractions of the guinea-pig ileum. However, there may be a lower receptor reserve in rat anococcygeus compared with the guin ea-pig ileum, since higher concentrations of agonists were necessary t o produce effects in the anococcygeus than in the guinea-pig ileum and S-PLA behaved as a partial agonist. The effect of NECA was antagonize d in rat anococcygeus and guinea-pig ileum by the mixed A(1)/A(2) rece ptor antagonist, 8-phenyltheophylline (pA(2), values of 6.8 and 6.9, r espectively). The selective A(1)-receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), also blocked the inhibitory response to NE CA in both tissues. Here, however, the pA(2) values (9.6 and 8.6, resp ectively) were slightly but significantly different. These values conf irm that the prejunctional adenosine receptors of the rat anococcygeus are of the A(1) type, and suggest that they are similar but not neces sarily identical to those of the guinea-pig ileum. The differing poten cies of DPCPX as an antagonist of NECA between the preparations may re flect a tissue-dependent variation in sensitivity to this antagonist.