Competitive and selective antagonism of P2Y1 receptors by N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate.
The antagonist activity of N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate (N6MABP) has been examined at the phospholipase C-coupled P2Y1 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 P2Y1 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 P2Y1 receptor, no antagonist effect of N6MABP was observed at the human P2Y2, human P2Y4 or rat P2Y6 receptors.
Boyer
J L
JL
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill 27599-7365, USA.
Mohanram
A
A
Camaioni
E
E
Jacobson
K A
KA
Harden
T K
TK
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D058472:Receptors, Purinergic P2Y1; D014407:Tumor Cells, Cultured; D014422:Turkeys
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546382:P2RY1 protein, human; C546384:P2ry1 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate