Biochemical mechanisms in 5-hydroxytryptamine-induced human platelet aggregation

Abstract

The activation of human platelets by 5-hydroxytryptamine (5-HT) is not accompanied by detectable release of ATP or TXB2. The process is unaffected by cyclooxygenase, thromboxane synthetase or combined cyclooxygenase/lipoxygenase inhibition (suprofen, indomethacin, R 19091, dazoxiben, N.D.G.A, BW755C, esculetin), indicating the absence of involvement of arachidonic acid metabolites. Transmembrane Ca2+-entry blockers (flunarizine, nifedipine, nimodipine) have no effect either, indicating that the activator calcium released by 5-HT comes from intracellular stores. The 5-HT-induced platelet activation is inhibited by stimulators of adenylate cyclase (PGE1, PGE2, isoprenaline, adenosine) and inhibitors of cAMP phosphodiesterase (papaverine, anagrelide, RA233), indicating that also for this type of platelet activation cAMP behaves as a unidirectional, inhibitory regulator.

Prostaglandin E1 and forskolin antagonize C-kinase activation in the human platelet

“…In the human platelet, 5-hydroxytryptamine induces shape changes and reversible aggregation without secretion [45]; the cellular free Ca2+ concentrations are raised [4]. Previous reports [4,46] showed that these phenomena were inhibited by PGE1 and FK in the concentration range in which they inhibit 5-hydroxytryptamine-induced increases in 40 kDa-and 20 kDaprotein phosphorylation and PA formation (Fig. 1).…”

The Serotonergic Mechanisms Are Not Involved in the Inhibitory Effect of Captopril on Rat Platelet Aggregation

“…One of the many factors which stimulate platelet aggregation is serotonin [7,8]. It amplifies platelet aggregation of rats and hu mans via 5-HT2 receptors [7,8], of which a selective antagonist is ketanserin [14], Thus we tried to determine whether the serotoner gic mechanisms play any role in the suppres sion of platelet aggregation evoked by capto pril.…”

“…It amplifies platelet aggregation of rats and hu mans via 5-HT2 receptors [7,8], of which a selective antagonist is ketanserin [14], Thus we tried to determine whether the serotoner gic mechanisms play any role in the suppres sion of platelet aggregation evoked by capto pril. In our experiments we demonstrated that captopril, in contrast to ketanserin, did not affect the amplifying effect of 5-HT ( fig.…”

“…collagen, ADP, thrombin, arachidonic acid, epinephrine or serotonin. The 5-hydroxytryptamine (5-HT, serotonin) system in rat blood platelets consists of a rel atively specific uptake mechanism for 5-HT, intracellular storage organelles and 5-HT2 receptors [7], The stimulation of 5-HT2 re ceptors induces a change of shape and the potentiation of platelet aggregation induced by many aggregating factors [8].…”

Influence of Ethanol and Serotonin on Rat Platelet Aggregation

“…It has been suggested that ethanol directly affects the function of blood platelet mem branes and acts indirectly by influencing plasma lipids or by changing the release and synthesis of some arachidonic acid deriva tives [2,5,6). Platelets contain serotonin (5-hydroxytryptamine, 5-HT) which evokes in vitro a reversible aggregation of human blood platelets [7] and amplifies platelet ag gregation in response to various agonists in cluding ADP, adrenaline, noradrenaline, collagen and the calcium ionophore A23187 [8], The amplification of platelet aggrega tion by 5-HT is inhibited by the selective 5-HT2 receptor antagonist ketanserin [9], Our previous studies demonstrated [10] that eth anol inhibits the uptake and enhances the release of 5-HT from rat blood platelets. In vitro, it inhibited the aggregation of blood platelets but did not change the potentiating action of 5-HT on ADP-induced aggrega tion.…”