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Phorbol Ester Enhancement of Neurotransmitter Release from Rat Brain Synaptosomes
Author(s) -
Nichols Robert A.,
Haycock John W.,
Wang James K. T.,
Greengard Paul
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb04137.x
Subject(s) - veratridine , neurotransmitter , synaptosome , protein kinase c , medicine , endocrinology , chemistry , glutamate receptor , acetylcholine , protein kinase a , calcium , biology , biochemistry , phosphorylation , receptor , central nervous system , sodium , organic chemistry , sodium channel
Neurotransmitter release from rat brain synaptosomes was measured following pretreatment with various phorbol esters. Ca 2+ ‐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 32 P 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 (P 2 ) or purified cortical synaptosomal fractions. The enhancement was found for all neurotransmitters (norepinephrine, acetylcholine, γ‐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 Ca 2+ ‐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.