Protein kinase C epsilon is involved in ethanol potentiation of glycine-gated Cl(-) current in rat neurons of ventral tegmental area.
Neuropharmacology
; 44(4): 493-502, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12646286
ABSTRACT
Previously, we demonstrated that ethanol potentiates glycine current (I(Gly)) in 35% of neurons freshly isolated from the ventral tegmental area (VTA) of rats (J. Pharmacol. Exp. Ther. 296 (2001) 77). In the present study, we examined the role of protein kinase C (PKC) in this action of ethanol on VTA neurons from young rats. Extracellular ethanol and intracellular ATP-gamma-S when applied separately potentiated I(Gly). However, ethanol potentiation of I(Gly) was significantly reduced in neurons dialyzed with 2 mM ATP-gamma-S. Phorbol-12-myristate-13-acetate (PMA, 10 nM), a PKC activator also increased I(Gly) and reduced ethanol potentiation of I(Gly). In addition, GF109203X (0.2 microM), a PKC inhibitor antagonized the potentiation effects produced either by PMA or by ethanol. Thus, ethanol potentiation of I(Gly) may be associated with PKC activation. While intracellular application of 1,2-bis(aminophenoxy)-ethane-N,N,N,N'-tetraacetic acid, a Ca(2+) chelator or Gö6976, an inhibitor of Ca(2+)-dependent PKC had no appreciable effect on ethanol potentiation of I(Gly), translocation inhibitor peptide (PKC(epsilon)-TIP) (500 nM) significantly reduced ethanol potentiation, an action the translocation inhibitor peptide negative control (PKC(epsilon)-TIP-NC) (500 nM) did not have. These results suggest that the activation of PKC(epsilon) isoenzyme contributes to ethanol-induced potentiation of GlyR function.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
/
Ativação do Canal Iônico
/
Trifosfato de Adenosina
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Área Tegmentar Ventral
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Canais de Cloreto
/
Etanol
/
Glicina
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article