CYCLIC-AMP ANTAGONIZES ADENOSINE-INDUCED INHIBITION OF GANGLIONIC TRANSMISSION

The mechanism of adenosine-induced inhibition of ganglionic transmissi on was investigated in the isolated superior cervical ganglion (SCG) o f the rat The inhibitory effect of adenosine on the postganglionic com pound action potential (CAP) was antagonized by pretreatment of gangli a with forskolin, isoproterenol (IPNE), arginine vasopressin (AVP), or papaverine, all of which are known to increase tissue CAMP level by d ifferent mechanisms. Furthermore, pretreatment of ganglia with the ade nylate cyclase inhibitor SQ 22,536, or the phosphodiesterase activator imidazole reversed the effects of IPNE and forskolin. Pretreatment wi th 8-bromo-cAMP, resulted in a marked antagonism of the adenosine-indu ced inhibition. By themselves, none of these drugs had any significant effect on the CAP. Adenosine slightly but significantly decreased the basal level of CAMP in untreated ganglia. Formation of CAMP induced b y IPNE was markedly reduced by adenosine. This was largely reversed in the presence of the adenosine A, receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) but not the A(2) receptor antagonist 3,7-di methyl-1-propargylxanthine (DPMX). We conclude that the inhibition of ganglionic transmission by adenosine involves reduction of CAMP format ion through activation of A(1) receptors. (C) 1998 Elsevier Science B. V.