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PROSTAGLANDIN ENDOPEROXIDES, THROMBOXANE A 2 AND ADENOSINE DIPHOSPHATE IN COLLAGEN‐INDUCED AGGREGATION OF RABBIT PLATELETS
Author(s) -
LEWIS G. P.,
WATTS I. S.
Publication year - 1982
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.1476-5381.1982.tb09183.x
Subject(s) - chemistry , prostaglandin , adenosine diphosphate , thromboxane , platelet , thromboxane a2 , thromboxane a synthase , arachidonic acid , biochemistry , creatine kinase , prostaglandin h2 , platelet aggregation inhibitor , medicine , endocrinology , platelet aggregation , enzyme , receptor , biology , aspirin
1 A bioassay technique is described for simultaneously monitoring rabbit platelet aggregation with measurement of thromboxane A 2 (TXA 2 ) and prostaglandins released in response to collagen or arachidonic acid (AA). 2 Five imidazole derivatives were examined as inhibitors of thromboxane synthetase and compared with the effect of the cyclo‐oxygenase inhibitor indomethacin; 1‐(7‐carboxyheptyl) imidazole was identified as the most potent and selective inhibitor of thromboxane synthetase and was used with indomethacin to investigate the relative contribution of the prostaglandin endoperoxides prostaglandin G 2 (PGG 2 )/PGH 2 and TxA 2 in mediating platelet aggregation induced by collagen or AA. 3 Platelet aggregation induced by a low concentration of collagen was abolished by indomethacin and carboxyheptylimidazole whilst in response to a high concentration or collagen only partial inhibition of aggregation occurred. 4 The contribution of adenosine diphosphate (ADP) released from platelets during collagen or AA‐induced aggregation was examined using the substrate/enzyme complex creatine phosphate/creatine phosphokinase (CP/CPK). The CP/CPK complex abolished aggregation induced by a low dose of collagen whilst aggregation to a high dose of collagen was only partially inhibited. 5 Aggregation induced by a high dose of collagen was abolished by a combination of CP/CPK with indomethacin or carboxyheptylimidazole. 6 AA‐induced aggregation was abolished by indomethacin. Carboxyheptylimidazole abolished aggregation induced by a low dose of AA but inhibition was surmounted with increasing concentrations of AA in the absence of TxA 2 formation. 7 PGH 2 ‐induced aggregation was unaffected by indomethacin and only partially inhibited by carboxyheptylimidazole. AA or PGH 2 ‐induced platelet aggregation was unaffected by CP/CPK. 8 In conclusion, aggregation of rabbit platelets induced by a low concentration of collagen was dependent on synergism between TxA 2 and ADP whilst at high concentrations of collagen, sufficient TxA 2 and ADP were released to induce aggregation independently of each other. 9 The small amounts of prostaglandin endoperoxides produced from endogenous arachidonate have apparently no direct pro‐aggregatory role. However, the relatively large amount which can be produced by a high concentration of exogenous AA when TxA 2 formation is prevented can cause aggregation of rabbit platelets.