Competitive and selective antagonism of P2Y₁receptors byN⁶-methyl 2′-deoxyadenosine 3′,5′-bisphosphate

The antagonist activity of N-6-methyl 2'-deoxyadenosine 3',5'-bisphosphate (N6MABP) has been examined at the phospholipase C-coupled P2Y(1) receptor of turkey erythrocyte membranes. N6MABP antagonized 2MeSATP-stimulated inositol phosphate hydrolysis with a potency approximately 20 fold greater than the previously studied parent molecule, adenosine 3',5'-bisphosphate. The P2Y(1) receptor antagonism observed with N6MABP was competitive as revealed by Schild analysis (pK(B) = 6.99 +/- 0.13). Whereas N6MABP was an antagonist at the human P2Y(1) receptor, no antagonist effect of N6MABP was observed at the human P2Y(2), human P2Y(4) or rat P2Y(6) receptors.