Phorbol ester enhancement of neurotransmitter release from rat brain synaptosomes.
Neurotransmitter release from rat brain synaptosomes was measured following pretreatment with various phorbol esters. Ca2+-dependent, evoked neurotransmitter release was increased by phorbol esters that were active in stimulating protein kinase C. Protein kinase C activation was demonstrated by increased incorporation of 32P into 87-kilodalton phosphoprotein, a specific substrate for that kinase. Inactive phorbol esters had no effect on neurotransmitter release or on the phosphorylation of 87-kilodalton phosphoprotein. The increased release was observed in either crude cortical synaptosomal fractions (P2) or purified cortical synaptosomal fractions. The enhancement was found for all neurotransmitters (norepinephrine, acetylcholine, gamma-aminobutyric acid, serotonin, dopamine, and aspartate), all brain regions (cerebral cortex, hippocampus, and corpus striatum), and all secretagogues (elevated extracellular K+ level, veratridine, or A23187) examined. It was also observed at all calcium concentrations present during stimulation of release. The phorbol ester enhancement of Ca2+-dependent release occurred whether or not calcium was present during pretreatment. These results indicate that stimulation of protein kinase C leads to an enhanced sensitivity of the stimulus-secretion coupling processes to calcium within the nerve terminal. The results support the possibility that presynaptic activation of protein kinase C modulates nerve terminal neurotransmitter release in the CNS.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D008433:Mathematics; D009638:Norepinephrine / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D010703:Phorbol Esters; D000001:Calcimycin; D014701:Veratridine; D011493:Protein Kinase C; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine