Effects of RP and SP diastereoisomers of adenosine 5'-O-(1-thiodiphosphate) on human platelets.
1 RP and SP diastereoisomers of adenosine 5'-O-(1-thiodiphosphate) ((R)-ADP-alpha-S and (S)-ADP-alpha-S), an adenosine 5'-diphosphate (ADP) analogue, were tested on intact human platelets. 2 Each diastereoisomer induced aggregation, (S)-ADP-alpha-S being 5 times more potent than (R)-ADP-alpha-S but they achieved only 75% of the maximal effect of ADP. 3 Aggregation induced by each diastereoisomer was competitively inhibited by ATP (50 microM). 4 Simultaneous addition of each diastereoisomer inhibited aggregation induced by ADP but not by 11 alpha, 9 alpha-epoxymethano prostaglandin H2, a stable endoperoxide analogue. Both diastereoisomers are therefore partial agonists at the ADP receptor mediating aggregation. 5 Unlike ADP, neither diastereoisomer inhibited prostaglandin E1 (PGE1)-stimulated adenylate cyclase, but each competitively inhibited the effect of aDP, with (S)-ADP-alpha-S again being 5 times more potent than (R)-ADP-alpha-S. 6 These are the first reported examples of ADP analogues to induce platelet aggregation without inhibiting PGE1-stimulated adenylate cyclase.
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009711:Nucleotides / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011463:Prostaglandins H / Q000378:metabolism; D013237:Stereoisomerism; D013873:Thionucleotides / Q000494:pharmacology*
D009711:Nucleotides; D011463:Prostaglandins H; D013873:Thionucleotides; C018444:adenosine 5'-O-(1-thiodiphosphate); D000244:Adenosine Diphosphate; D000262:Adenylyl Cyclases