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 K(m) and V(max) of platelet 5-HT high affinity uptake was investigated in vitro . 5-HT uptake, storage and release in response to increasing GVG conce ntrations (0-7.74 mM) at a constant incubation time (60 min) and in de pendence on time (0-90 min) at a constant GVG concentration (7.74 mM) remained unchanged. Concerning the high affinity 5-HT uptake, GVG (7.7 4 mM) caused a slight decrease of V(max) from 83.3 +/- 35.0 (SD) pmol 5-HT/108 pl./min to 77.0 +/- 33.4 (SD) pmol 5-HT/10(8) pl./min and a s ignificant elevation of K(m) 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 me ans 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 therap eutically nonrelevant high GVG concentrations. If platelets represent a model for 5-HT transport processes in presynaptic serotonergic neuro ns it is concluded that GVG has no effect on serotonergic activity.