EVIDENCE FOR AN A2/Ra ADENOSINE RECEPTOR IN THE GUINEA‐PIG TRACHEA

Abstract

1 An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea-pig trachea is of the A₁/R_i or A₂/R_a subtype. 2 Dose-response curves to adenosine and a number of 5′- and N⁶-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-N⁶-phenylisopropyladenosine (l-PIA) > adenosine > d-N⁶-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-β-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 A₂/R_a subtype of adenosine receptor and an intracellular purine-sensitive site, both of which mediate relaxation.