Phorbol ester,an activator of protein kinase C,enhances calcium-dependent release of sympathetic neurotransmitter |
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Authors: | Arun R Wakade Ravindra K Malhotra Taruna D Wakade |
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Institution: | (1) Department of Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, 11203 Brooklyn, New York, USA |
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Abstract: | Summary The effect of phorbol ester, phorbol 12,13-dibutyrate, was investigated on the overflow of tritium from 3H-noradrenaline-loaded sympathetic neurons of the isolated perfused salivary gland of the rat. Stimulation (1 Hz for 60 s)-evoked overflow of tritium was enhanced by phorbol ester. A significant enhancement was seen at 1 nmol/l, which increased to a maximum level (over 4-fold) at 30 nmol/l. The spontaneous overflow of radioactivity, however, was not affected by any concentration of phorbol ester. The facilitatory effect of phorbol ester on stimulation-evoked overflow was observed in the presence of inhibitors of neuronal and extraneuronal uptake as well as after removal of negative feedback inhibition of release by presynaptic alpha-adrenoceptors. Tyramine (7 mol/l for 10 min) caused a marked increase in the overflow of tritium in either the presence or absence of calcium. However, tyramine-induced overflow was not enhanced by phorbol ester. It is concluded that protein kinase C of sympathetic neurons is involved in an exocytotic release of the transmitter. |
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Keywords: | Phorbol ester Exocytosis Noradrenaline release Calcium Protein kinase C |
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