Evidence for the existence of the beta-endorphin-sensitive "epsilon-opioid receptor" in the brain: the mechanisms of epsilon-mediated antinociception.

Abstract

Recently, mu-, delta- and kappa-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-mu, non-delta and non-kappa. Based upon anatomical and binding studies in the brain, the sensitive site for an endogenous opioid peptide, beta-endorphin, has been postulated to account for the unique characteristics of the opioid receptor defined as a putative epsilon-opioid receptor. Many epsilon-opioid receptors are functionally coupled to G-proteins. The functional epsilon-opioid receptors in the brain are stimulated by bremazocine and etorphine as well as beta-endorphin, but not by selective mu-, delta- or kappa-opioid receptor agonists. Epsilon-opioid receptor agonists injected into the brain produce profound antinociception. The brain sites most sensitive to epsilon-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 epsilon-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 epsilon-opioid receptors, stimulates spinal delta2-opioid receptors for the production of antinociception. It is noteworthy that the epsilon-opioid receptor-mediated pain control system is different from that of other opioid systems. Although there appears to be no epsilon-selective ligand currently available, these findings provide strong evidence for the existence of the putative epsilon-opioid receptor and its unique function in the brain.

• Authors: M Narita, L F Tseng
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 76 Issue 3 Pg. 233-53 (Mar 1998) ISSN: 0021-5198 [Print] Japan
• PMID: 9593217 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Opioid Peptides
• Receptors, Opioid
• epsilon receptor
• Guanosine 5'-O-(3-Thiotriphosphate)
• beta-Endorphin
• Morphine
• GTP-Binding Proteins

Topics

• Amino Acid Sequence
• Animals
• Binding Sites
• Brain (anatomy & histology, drug effects, metabolism)
• Brain Stem (drug effects, metabolism)
• GTP-Binding Proteins (metabolism)
• Guanosine 5'-O-(3-Thiotriphosphate) (metabolism)
• Humans
• Molecular Sequence Data
• Morphine (pharmacology)
• Multigene Family
• Nociceptors (drug effects, metabolism)
• Opioid Peptides (chemistry, metabolism, pharmacology)
• Receptors, Opioid (drug effects, genetics, metabolism)
• Spinal Cord (drug effects, metabolism)
• beta-Endorphin (chemistry, metabolism, pharmacology)