期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 301, 期 1, 页码 119-128出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.301.1.119
关键词
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资金
- NIAAA NIH HHS [AA08757, AA00220] Funding Source: Medline
We have previously shown that short-term exposure to ethanol stimulates immunoreactive beta-endorphin (IR-beta-EP) release from hypothalamic neurons and that chronic ethanol exposure decreases the IR-beta-EP release from these neurons. The role of protein kinase C (PKC) in the ethanol-regulated beta-EP release from hypothalamic neurons has not been established. In this study, by using the primary cultures of hypothalamic neurons, we tested the effects of PKC stimulator phorbol ester 4beta-phorbol 12-myristate-13-acetate (PMA) and PKC inhibitor chelerythrine chloride on ethanol-induced IR-beta-EP release. Additionally, the effects of ethanol with or without PMA on expression and translocation of various PKC isoenzymes from cytosolic to membrane fraction were determined. PMA treatment increased IR-beta-EP release in a time- and dose-dependent manner. Acute ethanol treatment (3 h) increased, while chronic ethanol treatment (24 h) reduced, the magnitude of PMA-induced IR-beta-EP release. The stimulatory effect of acute ethanol on IR-beta-EP release was reduced by chelerythrine chloride. Determination of the effects of ethanol with or without PMA on seven different PKC isoenzymes (PKC-alpha, -betaI, -betaII, -gamma, -delta, -epsilon, and -zeta) revealed that the expression and translocation of only two PKC isoenzymes, PKC-delta and PKC-epsilon, were stimulated by acute treatment with ethanol. Acute ethanol also increased PMA-stimulated expression of these two isoenzymes. Chronic ethanol treatment reduced both basal and PMA-induced increase of PKC-delta and PKC-epsilon expression and translocation. These data provide evidence for the first time that ethanol-regulated IR-beta-EP secretion is controlled by the PKC system, possibly involving PKC-delta and PKC-epsilon isoenzymes.
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