The effect of trifluoperazine and R 24 571 on the K+-evoked release of 5-hydroxytryptamine from superfused...

The effect of trifluoperazine (10 microM) and of R 24571 (0.1 and 1.0 microM) on the release of [3H]-5-HT from superfused synaptosomes from rat brain was studied. Trifluoperazine, but not R 24571, produced a rapid transient increase in the basal efflux of [3H]-5-HT. This effect may be due to the cleavage of either Ca2+ or [3H]-5-HT from binding sites on the synaptosomal membrane. In contrast to the effects on the basal efflux of [3H]-5-HT, both drugs significantly inhibited the release of [3H]-5-HT in response to K+ depolarisation. This effect of trifluoperazine did not appear to be due to the known membrane stabilising effects of the drug, but appeared more likely to be due to the calmodulin-inhibiting effect of the drug. The results of this study support the view that calmodulin may be an important intermediate linking depolarisation with transmitter release in nerve terminals.