Activation of GABAA receptors suppresses ethanol-induced up-regulation of type 1 IP3 receptors†

Although type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs-1) are one of the major calcium channels to regulate intracellular Ca²⁺ concentration, there have been few available data how their expression is modified by long-term exposure to ethanol.

The present study attempted to clarify mechanisms of modification of IP3R-1 expression during long-term ethanol exposure by γ-aminobutyric acid (GABA)A receptors using mouse cerebral cortical neurons.

Long-term exposure to ethanol induced IP3R-1 protein up-regulation following increased expression of its mRNA. Pre-treatment with muscimol, a selective GABAA receptor agonist, significantly suppressed the ethanol-induced up-regulation of IP3R-1 protein and its mRNA, which was significantly abolished by bicuculline, a selective GABAA receptor antagonist.

These results indicate that GABAA receptors negatively regulate the ethanol-induced up-regulation of IP3R-1 protein expression via the suppression of gene transcription


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