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

The Japanese Journal of Pharmacology

Minoru Narita¹  Leon F. Tseng¹ 

[1] Department of Anesthesiology, Medical College of Wisconsin

关键词: ε-Opioid receptor;    β-Endorphin;    Descending enkephalinergic pathway;    Antinociception;   

DOI  :  10.1254/jjp.76.233

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(167)Cited-By(29)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 δ2-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.

【 授权许可】

Unknown