Title: EVIDENCE FOR AN A<sub>2</sub>/R<sub>a</sub> ADENOSINE RECEPTOR IN THE GUINEA‐PIG TRACHEA
Abstract: 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. 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. 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). The difference in potency between the stereoisomers d ‐ and l ‐PIA on the isolated trachea was at the most five fold. 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. 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. 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. 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.