The Sigma_1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids : Molecular, Physiological, and Behavioral Aspects

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著者

    • Monnet Francois P. MONNET Francois P.
    • Unite 705 de l'Institut National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 7157 du Centre National de la Recherche Scientifique, Universite de Paris V et VII, Hopital Lariboisiere-Fernand Widal
    • Maurice Tangui MAURICE Tangui
    • Unite 710 de l'Institut National de la Sante et de la Recherche Medicale, Ecole Pratique des Hautes Etudes, Universite de Montpellier II

抄録

Steroids synthesized in the periphery or <i>de novo</i> in the brain, so called 'neurosteroids', exert both genomic and nongenomic actions on neurotransmission systems. Through rapid modulatory effects on neurotransmitter receptors, they influence inhibitory and excitatory neurotransmission. In particular, progesterone derivatives like 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) are positive allosteric modulators of the γ-aminobutyric acid type A (GABA<sub>A</sub>) receptor and therefore act as inhibitory steroids, while pregnenolone sulphate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are negative modulators of the GABA<sub>A</sub> receptor and positive modulators of the <i>N</i>-methyl-<sc><font size = "-2">D</font></sc>-aspartate (NMDA) receptor, therefore acting as excitatory neurosteroids. Some steroids also interact with atypical proteins, the sigma (σ) receptors. Recent studies particularly demonstrated that the σ<sub>1</sub> receptor contributes effectively to their pharmacological actions. The present article will review the data demonstrating that the σ<sub>1</sub> receptor binds neurosteroids in physiological conditions. The physiological relevance of this interaction will be analyzed and the impact on physiopathological outcomes in memory and drug addiction will be illustrated. We will particularly highlight, first, the importance of the σ<sub>1</sub>-receptor activation by PREGS and DHEAS which may contribute to their modulatory effect on calcium homeostasis and, second, the importance of the steroid tonus in the pharmacological development of selective σ<sub>1</sub> drugs.<br>

収録刊行物

  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 100(2), 93-118, 2006-02-20 

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018240466
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    13478613
  • NDL 記事登録ID
    7821806
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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