2-Chloro-N(6)-cyclopentyladenosine, adenosine A(1) receptor agonist, antagonizes the adenosine A(3) receptor.

The potent adenosine A(1) receptor agonists, N(6)-cyclopentyladenosine (CPA) and 2-chloro-N(6)-cyclopentyladenosine (CCPA), were studied in Chinese hamster ovary (CHO) cells expressing the human adenosine A(3) receptor. CPA, but not CCPA, induced phosphoinositide turnover. CPA inhibited forskolin-stimulated cyclic AMP production (EC(50) value of 242+/-47 nM). CCPA competitively antagonized the effects of agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine) with K(B) value of 5.0 nM. CPA competition curves versus the A(3) antagonist radioligand [3H]PSB-11 (8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one) were right-shifted four-fold by 100 microM GTP, which had no effect on binding of CCPA or the antagonist MRS 1220 (N-[9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]benzene-acetamide). Thus, CCPA is a moderately potent antagonist (K(i)=38 nM) of the human A(3) adenosine receptor.