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A comparative study of the involvement of the prostaglandin H 2 /thromboxane A 2 pathway in intravascular platelet aggregation in guinea‐pigs and rats
Author(s) -
Mallarkey G.,
Smith G.M.
Publication year - 1985
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.1476-5381.1985.tb12926.x
Subject(s) - prostacyclin , thromboxane , thromboxane a synthase , chemistry , thromboxane a2 , guinea pig , platelet , prostaglandin , thromboxane b2 , pharmacology , prostaglandin e , in vivo , arachidonic acid , prostaglandin h2 , medicine , endocrinology , biochemistry , receptor , biology , enzyme , microbiology and biotechnology
1 The effects of indomethacin, dazoxiben and EPO45 on collagen‐induced platelet aggregation in vivo were studied in guinea‐pigs and rats to determine the involvement of the prostaglandin endoperoxide/thromboxane A 2 pathway in the aggregatory response. 2 Indomethacin and EPO45 (a thromboxane receptor antagonist) partially inhibited platelet aggregation in rats. It was concluded that only one third of the aggregatory response to collagen was mediated by the products of cyclo‐oxygenase conversion of arachidonic acid. 3 In rats, dazoxiben was inactive although the conversion of the prostaglandin endoperoxides to thromboxane A 2 was inhibited (measured as thromboxane B 2 ). 6‐keto PGF 1α was detected in plasma after collagen was injected into dazoxiben‐treated rats. In this species therefore, the endoperoxides have significant aggregatory activity whilst the apparent increase in the level of prostacyclin was not sufficient to have any anti‐aggregatory effect. 4 All three drugs were active in the guinea‐pig. About 60% of the aggregatory response to collagen was due to the products of the cyclo‐oxygenase pathway, the main mediator being thromboxane A 2 . 5 In guinea‐pigs, dazoxiben also elevated 6‐keto PGF 1α in the plasma after an injection of collagen. However, this apparent increase in prostacyclin production did not contribute to the anti‐aggregatory effect.