Neurotransmitter release is triggered by an elevated level of free calcium and thus represents a crucial event in synaptic transmission. However the biochemical processes involved in calcium influx and calcium-dependent transmitter release are not known. Ethanol can alter the mobilization of calcium in a number of cells systems including synaptic transmission. The calcium/phospholipid-dependent protein kinase, protein kinase C, is highly localized in neuronal tissue and in particular presynaptic nerve terminals. I have examined the role of activation or inhibition of protein kinase C on the release of noradrenaline from rat isolated atria preloaded with [3-H]- noradrenaline. It was found that activation of protein kinase C by phorbol 12-myristate 13-acetate caused a concentration-dependent enhancement of membrane depolarization induced (electrical field stimulation or high potassium) release of noradrenaline. Whereas polymyxin B, an inhibitor of protein kinase C reduced noradrenaline release evoked by either electrical field stimulation or high potassium. In contrast, non-exocytotic release of noradrenaline evoked by tyramine was not altered by phorbol 12-myristrate 13-acetate. Polymyxin B only at a high concentration caused a slight reduction in tyramine-induced outflow of radioactivity. The findings suggest that protein kinase C may play a role in the exocytotic release of noradrenaline but not due to displacement. Ongoing studies will examine the effect of acute and chronic ethanol treatment on the calcium/protein kinase systems involved in neurotransmission.
