Dual effects of 5-hydroxytryptamine on stable analogue of thromboxane A2-induced aggregation and release reaction in rabbit platelets.

AIM: To study the effects of 5-hydroxytryptamine (5-HT) on stable analogue of thromboxane A2 (STA2)-induced platelet shape, aggregation, and release reaction. METHODS: Platelet shape change and aggregation were quantified by the light transmission through platelet-rich plasma (PRP). Release reaction was evaluated by the amount of ATP in the medium and cytosolic-free Ca2+ was measured by fluorescent imaging. RESULTS: (1) STA2 0.3-3 mumol.L-1-induced shape change followed by aggregation. When STA2 1 or 3 mumol.L-1 was added to PRP, the release reaction was occurred. Pretreatment of PRP with 5-HT 3 mumol.L-1, the shape change by STA2 was abolished and the aggregation by STA2 0.3 mumol.L-1 was enhanced (P < 0.01), STA2 1 or 3 mumol.L-1-induced aggregation was not affected, but the release reaction was partially suppressed (P < 0.01). (2) STA2 0.3 mumol.L-1-induced [Ca2+]i elevation was further increased by 5-HT pretreatment, but the [Ca2+]i mobilizations by STA2 3 mumol.L-1 was decreased by 5-HT, especially the peak level. (3) The aggregation without release reaction was increased from 3.4 +/- 2.1 to 25.6 +/- 1.8% (P < 0.01) with 10 s interval and the enhancement was declined with the prolongation of the intervals. The aggregation with release reaction was not affected by changing the intervals, but the release reaction was decreased in the same treatment. CONCLUSION: The dual effects of 5-HT on STA2-induced aggregation and release reaction and the molecular mechanism of this effect was probably through the regulative action of 5-HT on [Ca2+]i mobilization by STA2.