Inhibition by miltirone of up-regulation of GABA_A receptor α₄ subunit mRNA by ethanol withdrawal in hippocampal neurons

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• 作者：Mostallino ; Maria Cristina ; Mascia ; Maria Paola ; Pisu ; Maria Giuseppina ; Busonero ; Fabio ; et. al.
• 关键词：Miltirone ; GABA_A receptor ; Ethanol withdrawal ; Dependence
• 刊名：European Journal of Pharmacology
• 出版年：2004
• 出版时间：June 28, 2004
• 年：2004
• 卷：494
• 期：2-3
• 页码：83-90
• 全文大小：402 K

文摘

Miltirone, a tanshinone isolated from the root of Salvia miltiorrhiza, has been characterized as a low-affinity ligand for central benzodiazepine receptors. We have now shown that this compound bound with low affinity (micromolar range) to central benzodiazepine recognition sites but did not interact with peripheral benzodiazepine receptors. It failed to potentiate Cl⁻ currents induced by γ-aminobutyric acid (GABA) both in Xenopus oocytes expressing recombinant human GABA_A receptors and in cultured rat hippocampal pyramidal cells, but it inhibited the ability of diazepam to potentiate the effect of GABA in these systems. Miltirone (1–10 μM) also partially inhibited the increase in the abundance of the mRNA for the α₄ subunit of the GABA_A receptor induced by ethanol withdrawal in cultured hippocampal neurons. These results suggest that miltirone might ameliorate the symptoms associated with discontinuation of long-term administration of ethanol or of other positive modulators of the GABA_A receptor.