Effect of vigabatrin (GVG) on serotonin (5-HT) uptake and release of human platelets in vitro.
In platelets from healthy persons the effect of gamma-vinyl-GABA (GVG) on 5-HT uptake, storage, release and the kinetic parameters Km and Vmax of platelet 5-HT high affinity uptake was investigated in vitro. 5-HT uptake, storage and release in response to increasing GVG concentrations (0-7.74 mM) at a constant incubation time (60 min) and in dependence on time (0-90 min) at a constant GVG concentration (7.74 mM) remained unchanged. Concerning the high affinity 5-HT uptake, GVG (7.74 mM) caused a slight decrease of Vmax from 83.3 +/- 35.0 (SD) pmol 5-HT/10(8) pl./min to 77.0 +/- 33.4 (SD) pmol 5-HT/10(8) pl./min and a significant elevation of Km from 4.2 +/- 1.1 (SD) x 10(-7) M to 6.7 +/- 1.8 (SD) x 10(-7) M (P < 0.002) to about 160% of the control. This means a competitive inhibition of 5-HT uptake induced by GVG. Altogether, the effects of GVG on platelet 5-HT transport appear to be weak. An alteration of the platelet 5-HT system was demonstrated only at therapeutically nonrelevant high GVG concentrations. If platelets represent a model for 5-HT transport processes in presynaptic serotonergic neurons it is concluded that GVG has no effect on serotonergic activity.
Rolf
L H
LH
University of Münster, Department of Neurology, Germany.
Voges
B
B
D000328:Adult; D000614:Aminocaproates / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects*; D012701:Serotonin / Q000097:blood*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D020888:Vigabatrin