COMPETITIVE AND SELECTIVE ANTAGONISM OF P2Y(1) RECEPTORS BY N-6-METHYL 2'-DEOXYADENOSINE 3',5'-BISPHOSPHATE

The antagonist activity of N-6-methyl 2'-deoxyadenosine 3',5'-bisphosp hate (N6MABP) has been examined at the phospholipase C-coupled P2Y(1) receptor of turkey erythrocyte membranes. N6MABP antagonized 2MeSATP-s timulated inositol phosphate hydrolysis with a potency approximately 2 0 fold greater than the previously studied parent molecule, adenosine 3',5'-bisphosphate. The P2Y(1) receptor antagonism observed with N6MAB P was competitive as revealed by Schild analysis (pK(B) = 6.99 +/- 0.1 3). Whereas N6MABP was an antagonist at the human P2Y(1) receptor, no antagonist effect of N6MABP was observed at the human P2Y(2), human P2 Y(4) or rat P2Y(6) receptors.