Specific Inhibition of ADP-Induced Platelet Responses by 2-n-Amylthio Amp

“Primary” aggregation responses to ADP are blocked by 2-n-amylthio AMP (nAmSAMP)*, apparently competitively (K_i ≃ 10 μM). Shape change is inhibited by higher concentrations (> 0.1 mM). nAmSAMP has a modest inhibitory effect on platelet responses to ionophore Lilly A23187 and a greater effect on responses to collagen and blocks secretion and secondary aggregation induced by ADP, adrenaline, arachidonic acid, PGG₂, and synthetic analogues of PGE₂ and PGH₂-nAmSAMP is a much less potent inhibitor than adenosine against all stimulants apart from ADP and is qualitatively unlike adenosine in the following respects:1. primary aggregation responses to the above agents (except ADP) and to serotonin and vasopressin are unaffected;2. inhibition is not increased by preincubation;3. inhibition is not decreased by an inhibitor of adenylate cyclase, SQ22536 (9-[tetrahydro-2-furyl]-adenine);4. basal levels of platelet cyclic AMP are unaffected. We conclude that, unlike adenosine, nAmSAMP does not inhibit platelet responses by stimulating adenylate cyclase. nAmSAMP appears to be a “specific” competitive antagonist of ADP and should therefore be useful in clarifying the role of ADP in platelet reactions.