Phorbol ester, an activator of protein kinase C, enhances calcium-dependent release of sympathetic neurotransmitter.
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 mumol/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.
Wakade
A R
AR
Malhotra
R K
RK
Wakade
T D
TD
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012469:Salivary Glands / Q000201:enzymology; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014439:Tyramine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine; D014439:Tyramine