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• W2039881330 startingPage "967" @default.
• W2039881330 abstract "The brain is particularly sensitive to alcohol during its growth spurt period. To better understand the mechanism(s) involved, we studied the effects of ethanol on neurons freshly dissociated from the ventral tegmental area (VTA) in neonatal rats. Ethanol enhanced (35%) or depressed (45%) glycine-induced responses in VTA neurons (Ye et al., 2001a, 2001b). In this report, we investigated the role of protein kinase C (PKC) and protein kinase A (PKA) in ethanol-induced inhibition of glycine-activated current, using whole-cell patch-clamp technique. Ethanol inhibited glycine-activated current when it was coapplied with the agonist. This inhibition was enhanced when neurons were pretreated with ethanol before the subsequent coapplication of ethanol and glycine. Ethanol's inhibition of glycine-activated currents increased with the length of ethanol pretreatment time (ranging from 1 to 30 s), and reached the maximum at 30 s. However, this enhanced inhibition was not seen in the absence of internal ATP. In addition, phorbol-12-myristate-13-acetate (PMA, 100 nM), a PKC activator, markedly inhibited glycine-activated current. Blockade of PKC by chelerythrine or by PKC inhibitor peptide significantly attenuated ethanol-induced inhibition. Although partial increase of PKC activity by 1 nM PMA enhanced ethanol inhibition, pretreatment of ethanol did not increase ethanol inhibition after the neurons were treated with 100 nM PMA. These data suggest that ethanol and PKC share the same pathway to suppress glycine receptors. H-89 (1 microM), a selective PKA inhibitor, did not alter glycine-activated current or ethanol inhibition. Our observations suggest that activation of PKC (but not PKA) contributes to ethanol-induced inhibition of glycine receptors." @default.
• W2039881330 created "2016-06-24" @default.
• W2039881330 creator A5007583142 @default.
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• W2039881330 date "2002-03-01" @default.
• W2039881330 modified "2023-10-12" @default.
• W2039881330 title "Protein Kinase C Modulation of Ethanol Inhibition of Glycine-Activated Current in Dissociated Neurons of Rat Ventral Tegmental Area" @default.
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• W2039881330 doi "https://doi.org/10.1124/jpet.300.3.967" @default.
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