title: μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids.
abstract: The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-perspective, we review the recently identified, functional MOR isoform subclass, which consists of six transmembrane helices (6 TM) and may play an important role in MOR signaling. There is evidence that 6 TM MOR signals through very different cellular pathways and may mediate excitatory cellular effects rather than the classic inhibitory effects produced by the stimulation of the major (7 TM) isoform. Therefore, the development of 6 TM and 7 TM MOR selective compounds represents a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.
authors.affiliation: Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Marino
authors.initials: M
authors.lastname: Convertino
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec H3A 0G1, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Samoshkin
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC 27599, USA.
authors.forename: Josee
authors.initials: J
authors.lastname: Gauthier
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gold
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC 27599, USA. Electronic address: bill_maixner@dentistry.unc.edu.
authors.forename: William
authors.initials: W
authors.lastname: Maixner
authors.affiliation: Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC 27599, USA. Electronic address: dokh@unc.edu.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.affiliation: The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec H3A 0G1, Canada. Electronic address: luda.diatchenko@mcgill.ca.
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D006801:Humans; D011487:Protein Conformation; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu
keywords: 6TM MOR isoform; Drug discovery; Review; μ-Opioid receptor