Evidence for the Existence of the β-Endorphin-Sensitive "ε-Opioid Receptor" in the Brain: The Mechanisms of ε-Mediated Antinociception

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Recently, μ-, δ- and κ-opioid receptors have been cloned and relatively well-characterized. In addition to three major opioid receptor types, more extensive studies have suggested the possible existence of other opioid receptor types that can be classified as non-μ, non-δ and non-κ. Based upon anatomical and binding studies in the brain, the sensitive site for an endogenous opioid peptide, β-endorphin, has been postulated to account for the unique characteristics of the opioid receptor defined as a putative ε-opioid receptor. Many ε-opioid receptors are functionally coupled to G-proteins. The functional ε-opioid receptors in the brain are stimulated by bremazocine and etorphine as well as β-endorphin, but not by selective μ-, δ- or κ-opioid receptor agonists. ε-Opioid receptor agonists injected into the brain produce profound antinociception. The brain sites most sensitive to ε-agonist-induced antinociception are located in the caudal medial medulla such as the nucleus raphe obscures, nucleus raphe pallidus and the adjacent midline reticular formation. The stimulation of ε-opioid receptors in the brain facilitates the descending enkephalinergic pathway, which probably originates from the brainstem terminating at the spinal cord. The endogenous opioid Met-enkephalin, released in the spinal cord by activation of supraspinal ε-opioid receptors, stimulates spinal δ<SUB>2</SUB>-opioid receptors for the production of antinociception. It is noteworthy that the ε-opioid receptor-mediated pain control system is different from that of other opioid systems. Although there appears to be no ε-selective ligand currently available, these findings provide strong evidence for the existence of the putative ε-opioid receptor and its unique function in the brain.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 76(3), 233-253, 1998-03

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10008191728
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    00215198
  • NDL 記事登録ID
    4440443
  • 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  CJP引用  NDL  J-STAGE 
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