Potentiation by adenosine of histamine-induced bronchospasm in anaesthetized guinea-pig: Receptor subtype/s involved

A potentiating effect by adenosine on the bronchocontractile response to histamine has been previously described in a guinea-pig model (Breschi et al. [1994] Pharmacology 49:42-51). In the present study, the subtype(s) of purinergic receptors involved in this modulatory effect of the nucleoside have been investigated. A possible role for P2 receptors or for the putative P3 receptor subtype was excluded because of the very poor modulatory effect of the P2 agonist alpha,beta-methylene ATP when compared with the effects of all the P1 agonists tested, with the exception of 5'-N-Methyl-N-6-(3-iodobenzyl)adenosine. The order of potency revealed for the P1 agonists was R-N-6-[2-phenylisopropyl]adenosine (R-PIA) = 5'-N-methylcarboxamidoadenosine > N-6-2-(4-aminophenyl)ethyladenosine greater than or equal to adenosine and in the presence of R-PIA, a significantly greater maximal effect was observed. Among the adenosine receptor antagonists evaluated, the A(2) antagonist 3,7-dimethyl-1-propargylxanthine even increased the effect of adenosine and no influence was evident with the reported A(2B) antagonist enprofylline. A significant reduction of the potentiating activity of adenosine was, on the contrary, obtained with the nonselective blocker theophylline or the A(1) antagonist DPCPX. In conclusion, the above data suggest that the potentiation of histamine-induced bronchoconstriction by adenosine is mediated by the stimulation of A(1) receptors. Drug Dev. Res. 45:17-22, 1998. (C) 1998 Wiley-Liss, Inc.