Evidence for an A2/Ra adenosine receptor in the guinea-pig trachea.

1 An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea-pig trachea is of the A(1)/R(i) or A(2)/R(a) subtype.2 Dose-response curves to adenosine and a number of 5'- and N(6)-substituted analogues were constructed for the isolated guinea-pig trachea, contracted with carbachol.3 The 5'-substituted analogues of adenosine were the most potent compounds tested, the order of potency being 5'-N-cyclopropylcarboxamide adenosine (NCPCA) > 5'-N-ethylcarboxamide adenosine (NECA) > 2-chloroadenosine > L-N(6)-phenylisopropyladenosine (L-PIA) > adenosine > D-N(6)-phenylisopropyladenosine (D-PIA).4 The difference in potency between the stereoisomers D- and L-PIA on the isolated trachea was at the most five fold.5 Responses to low doses of adenosine and its analogues were attenuated after treatment with either theophylline or 8-phenyltheophylline. The responses to 2-chloroadenosine were affected to a lesser extent than were those to the other purines.6 Adenosine transport inhibitors, dipyridamole and dilazep, potentiated responses to adenosine, did not affect those to NCPCA, NECA, L-PIA and D-PIA but significantly reduced the responses to high doses of 2-chloroadenosine.7 Relaxations evoked by 9-beta-D-xylofuranosyladenosine which can activate intracellular but not extracellular adenosine receptors, were attenuated by dipyridamole but unaffected by 8-phenyltheophylline.8 The results support the existence of an extracellular A(2)/R(a) subtype of adenosine receptor and an intracellular purine-sensitive site, both of which mediate relaxation.