Facilitatory effect of trifluoperazine on adrenergic transmitter release from rat portal veini

To determine the relationship between calmodulin (CaM) and transmitter release, the effects of trifluoperazine (TFP) on adrenergic transmission in rat portal vein preparations prelabelled with [3H]norepinephrine ([3H]NE) were studied. It was found that the CaM inhibitor TFP, at a concentration of 100 ymol/L, significantly facilitated both the spontaneous and high-K+ (65 mmol/L) evoked release of [3H] NE. Diazepam. a Ca2+/CaM-dependent kinase system inhibitor. exhibited the same actions as TFP. The facilitatory effect of TFP on [3H]NE release was abolished in Ca2+-free. EGTA-containing buffer.and attenuated by MnCl2 5 mmol/L and tetrodotoxin (TTX) 3 vmol/L. 2,4-Dinitrophenol, an ATP production inhibitor, had no effect on [3H]NE release when administered alone. but it did inhibit the TFP-evoked [3H]NE release. The facilitatory effect of TFP was not inhibited by cocaine. while that of tyramine was. TFP inhibited CaM activity in a dose-dependent manner. and complete inhibition was observed at 80 ymol/L, a concentration needs by [3H]NE release facijitatory effect. The pharmacological mechanism of the facilitatory effect of TFP is thought to be the result from its specific inhibition of CaM, without any involvement of the Ca2+ channel blocking effect. Consequently. it is suggested that CaM plays an important role not only in producing exocytosis as demonstrated by DeLorenzo and others. but also in controlling transmitter release. This action is Ca2+ and energy dependent process.