Characterization of a specific adenosine receptor on human lymphocytes.
We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 micrometer to 10 micrometer) increased lymphocytes cAMP levels in a dose-dependent fashion with a maximal (10 micrometer) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 micrometer. Adenosine appears to act on the cell surface since 1) 2-chloroadenosine, a poorly metabolized adenosine analogue, was as active as adenosine and 2) dipyridamole, which markedly inhibited [3H]-adenosine uptake by human lymphocytes, did not affect adenosine-induced accumulation of cAMP. The specificity of the adenosine effect was established by showing that the methylxanthine derivatives, theophylline and 3-isobutyl-1-methylxanthine (IBMX), specifically block the accumulation of cAMP in lymphocytes induced by adenosine. Theophylline is a competitive inhibitor of the effect of adenosine, with an estimated dissociation constant of theophylline-receptor complex of about 6.3 X 10(-7) M. The results suggest that adenosine increases the intracellular cAMP content of lymphocytes as a result of its interaction with a specific membrane receptor which results in the activation of adenylate cyclase.
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism*; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D004176:Dipyridamole; D000242:Cyclic AMP; D000241:Adenosine