ADENOSINE RECEPTOR-MEDIATED RELAXATION OF GUINEA-PIG PRECONTRACTED, ISOLATED TRACHEA

1 We have investigated the pharmacological profile of the adenosine receptor mediating relaxation of the carbachol pre-contracted guinea-pig trachea. 2 5'-N-Ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine elicited concentration-dependent relaxations with pD(2) (-log(10) half-maximal values) of 6.37 +/- 0.04 and 5.25 +/- 0.09, with maximal relaxations of 73 +/- 7 and 208 +/- 38%, respectively. In the presence of 10 mu M NECA, 2-chloroadenosine was able to relax the tissue further with a pot value of 4.74 +/- 0.11 and a maximal response of 252 +/- 68%. 3 CGS 21680, APEC and adenosine failed to elicit significant relaxations of precontracted tracheal rings at concentrations below 10 mu M. At 10 mu M, adenosine analogues elicited relaxations with the following order of magnitude (% relaxation): 2-chloroadenosine (75 +/- 16%) = NECA (69 +/- 16%) > APEC(25 +/- 8%) > CGS 21680 (11 +/- 2%) > adenosine (6 +/- 4%). 4 NECA-induced relaxation of precontracted trachea was antagonized by adenosine receptor antagonists with the rank order of apparent affinity (K-i, nM): PD 115,199 (27 +/- 8)=XAC (43 +/- 11) > CP 66,713(285 +/- 89)=DPCPX (316 +/- 114). 5 We conclude that the adenosine analogue-induced relaxation of guinea-pig tracheal rings fails to fit into the current classification of A(2) adenosine receptors.