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5‐Hydroxytryptamine and arachidonic acid metabolites modulate extensive platelet activation induced by collagen in cats in vivo
Author(s) -
Clerck F.,
Loots W.,
Somers Y.,
Beetens J.,
Wouters L.,
Wynants J.,
Janssen P.A.J.
Publication year - 1990
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.1476-5381.1990.tb12982.x
Subject(s) - platelet , chemistry , thromboxane , ketanserin , platelet activation , thromboxane b2 , pharmacology , aspirin , prostaglandin , medicine , endocrinology , cyclooxygenase , in vivo , thromboxane a2 , receptor , biochemistry , serotonin , biology , 5 ht receptor , enzyme , microbiology and biotechnology
1 The pathways contributing to the platelet adhesion/aggregation reaction elicited by collagen microfibrils, administered to cats in vivo , were analysed. 2 The intra‐aortic infusion of collagen (100 μg kg −1 in 1 min) caused an extensive activation of platelets, as evidenced by the time‐dependent drop of free platelet numbers in whole blood, and the increases of 5‐hydroxyindoles (5‐HI), 5‐hydroxytryptamine (5‐HT) and thromboxane B 2 (TXB 2 ) levels in plasma, prepared from effluent venous blood sampled from the inferior caval vein. 3 5‐HT 2 receptor blockade with ketanserin (0.63 mg kg −1 i.v., 10 min) and cyclo‐oxygenase inhibition with aspirin (10 mg kg −1 i.v., 10 min) slightly attenuated the peak reduction of free platelets in whole blood in response to collagen without affecting changes in plasma 5‐HI. Aspirin, but not ketanserin, reduced the collagen‐induced changes in plasma TXB 2 , prostaglandin E 2 (PGE 2 ) and 6K‐PGF 1α . 4 Dual TXA 2 synthetase inhibition/TXA 2 ‐prostaglandin endoperoxide receptor antagonism with ridogrel (5 mg kg −1 i.v., 10 min) halved the drop in free platelets, reduced the release of platelet 5‐HI, inhibited the increase in plasma TXB 2 and elevated that of 6K‐PGF 1α and PGE 2 in response to collagen. 5 Combined treatment with ketanserin and aspirin reduced the collagen‐induced drop of free platelets and the release of platelet 5‐HI to a similar extent as ridogrel alone; plasma prostanoids were affected as with aspirin alone. 6 Combined administration of ketanserin and ridogrel virtually eliminated the collagen‐induced platelet adhesion/aggregation response and release of 5‐HI; prostanoids were affected as with ridogrel alone. 7 The results indicate that the interplay between 5‐HT and arachidonic acid metabolites is causally involved in the platelet reaction to activation induced by collagen in cats in vivo .