5-Hydroxytryptamine and arachidonic acid metabolites modulate extensive platelet activation induced by collagen in cats in vivo.
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 micrograms 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 B2 (TXB2) levels in plasma, prepared from effluent venous blood sampled from the inferior caval vein. 3. 5-HT2 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 TXB2, prostaglandin E2 (PGE2) and 6K-PGF1 alpha. 4. Dual TXA2 synthetase inhibition/TXA2-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 TXB2 and elevated that of 6K-PGF1 alpha and PGE2 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. 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.
De Clerck
F
F
Department of Haematology, Janssen Research Foundation, Beerse, Belgium.
Loots
W
W
Somers
Y
Y
Beetens
J
J
Wouters
L
L
Wynants
J
J
Janssen
P A
PA
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D002415:Cats; D003094:Collagen / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010421:Pentanoic Acids / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010421:Pentanoic Acids; D011725:Pyridines; D011982:Receptors, Prostaglandin; D016718:Arachidonic Acid; D012701:Serotonin; D003094:Collagen; D007650:Ketanserin; D013930:Thromboxane-A Synthase; C060219:ridogrel; D001241:Aspirin