μ-Opioid receptor 6-transmembrane isoform: a potential therapeutic target for new effective opioids
Identifieur interne : 000731 ( Main/Exploration ); précédent : 000730; suivant : 000732μ-Opioid receptor 6-transmembrane isoform: a potential therapeutic target for new effective opioids
Auteurs : Marino Convertino ; Alexander Samoshkin [Canada] ; Josee Gauthier ; Michael S. Gold ; William Maixner ; Nikolay V. Dokholyan ; Luda Diatchenko [Canada]Source :
- Progress in neuro-psychopharmacology & biological psychiatry [ 0278-5846 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Récepteur mu.
- métabolisme : Récepteur mu.
- pharmacologie : Analgésiques morphiniques.
- Animaux, Conformation des protéines, Humains, Isoformes de protéines.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Receptors, Opioid, mu.
- chemical , metabolism : Receptors, Opioid, mu.
- chemical , pharmacology : Analgesics, Opioid.
- Animals, Humans, Protein Conformation, Protein Isoforms.
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 (6TM) and may play an important role in MOR signaling. There is evidence that 6TM 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 (7TM) isoform. Therefore, the development of 6TM and 7TM MOR selective compounds represent a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.
Url:
DOI: 10.1016/j.pnpbp.2014.11.009
PubMed: 25485963
PubMed Central: 4646084
Affiliations:
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Le document en format XML
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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 (6TM) and may play an important role in MOR signaling. There is evidence that 6TM 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 (7TM) isoform. Therefore, the development of 6TM and 7TM MOR selective compounds represent a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.</p></div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><noCountry><name sortKey="Convertino, Marino" sort="Convertino, Marino" uniqKey="Convertino M" first="Marino" last="Convertino">Marino Convertino</name><name sortKey="Dokholyan, Nikolay V" sort="Dokholyan, Nikolay V" uniqKey="Dokholyan N" first="Nikolay V." last="Dokholyan">Nikolay V. Dokholyan</name><name sortKey="Gauthier, Josee" sort="Gauthier, Josee" uniqKey="Gauthier J" first="Josee" last="Gauthier">Josee Gauthier</name><name sortKey="Gold, Michael S" sort="Gold, Michael S" uniqKey="Gold M" first="Michael S." last="Gold">Michael S. Gold</name><name sortKey="Maixner, William" sort="Maixner, William" uniqKey="Maixner W" first="William" last="Maixner">William Maixner</name></noCountry><country name="Canada"><region name="Québec"><name sortKey="Samoshkin, Alexander" sort="Samoshkin, Alexander" uniqKey="Samoshkin A" first="Alexander" last="Samoshkin">Alexander Samoshkin</name></region><name sortKey="Diatchenko, Luda" sort="Diatchenko, Luda" uniqKey="Diatchenko L" first="Luda" last="Diatchenko">Luda Diatchenko</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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