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EFFECTS OF R P AND S P DIASTEREOISOMERS OF ADENOSINE 5′‐O‐(1‐THIODIPHOSPHATE) ON HUMAN PLATELETS
Author(s) -
CUSACK N.J.,
HOURANI S.M.O.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb10437.x
Subject(s) - diastereomer , adenylate kinase , adenosine , cyclase , adenosine diphosphate , stereochemistry , platelet , chemistry , alpha (finance) , prostaglandin , receptor , biochemistry , platelet aggregation , biology , medicine , construct validity , nursing , patient satisfaction , immunology
1 R P and S P diastereoisomers of adenosine 5′‐O‐(1‐thiodiphosphate) ((R)‐ADP‐β‐S and (S)‐ADP‐β‐S), an adenosine 5′‐diphosphate (ADP) analogue, were tested on intact human platelets. 2 Each diastereoisomer induced aggregation, (S)‐ADP‐α‐S being 5 times more potent than (R)‐ADP‐α‐S but they achieved only 75% of the maximal effect of ADP. 3 Aggregation induced by each diastereoisomer was competitively inhibited by ATP (50 μm) 4 Simultaneous addition of each diastereoisomer inhibited aggregation induced by ADP but not by 11α, 9α‐epoxymethano prostaglandin H 2 , a stable endoperoxide analogue. Both diastereoisomers are therefore partial agonists at the ADP receptor mediating aggregation. 5 Unlike ADP, neither diastereoisomer inhibited prostaglandin E 1 (PGE 1 ‐stimulated adenylate cyclase, but each competitively inhibited the effect of ADP, with (S)‐ADP‐α‐S again being 5 times more potent than (R)‐ADP‐α‐S. 6 These are the first reported examples of ADP analogues to induce platelet aggregation without inhibiting PGE 1 ‐stimulated adenylate cyclase.