Pharmacological study of adenosine and related compounds on isolated guinea pig reachea: evidence for more than on type of purine receptor

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Abstract
Relaxation of guinea pig trachea in response to adenine, adenosine, ATP, ADP, 5''-AMP, 3'',5''-ADP, CoA and 2-chloroadenosine appears to be mediated by more than 1 type of receptor. Relaxation produced by the phosphorylated derivatives (nucleotides) was partially blocked by the prostaglandin [PG] synthetase inhibitor indomethacin (0.28-5.6 .mu.M). Responses to adenine, adenosine and 2-chloroadenosine were largely insensitive to indomethacin blockade. The adenosine uptake blocker dipyridamole (2,5 .mu.M) potentiated inhibitory response to adenosine > 5''-AMP > ATP > 3'',5''-ADP .gtoreq. ADP > CoA = acetyl CoA but not responses to adenine, 2-chloroadenosine, or l-noradrenaline [norepinephrine]. The putative purine receptor antagonists aminophylline, metoclopramide, quinidine, phentolamine and 2,2''-pyridylisatogen tosylate failed to specifically block responses to adenosine, CoA or ATP. In the presence of dipyridamole and indomethacin, aminophylline (5 and 10 .mu.M) attenuated responses to low concentrations of adenosine, 2-chloroadenosine, ATP and CoA but not adenine. Adenosine and in particular its phosphorylated derivatives have complex pharmacological actions in tracheal smooth muscle. Studies with dipyridamole, indomethacin and aminophylline alone and in combination suggest the presence of an adenosine specific receptor mechanism which mediates relaxation independent of PG and which is activated by ATP, CoA and 2-chloroadenosine but not adenine.