Literature DB >> 30913037

Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.

Ning-Sheng Cai1, César Quiroz1, Jordi Bonaventura2, Alessandro Bonifazi3, Thomas O Cole4, Julia Purks5, Amy S Billing6, Ebonie Massey6, Michael Wagner6, Eric D Wish6, Xavier Guitart1, William Rea1, Sherry Lam2, Estefanía Moreno7, Verònica Casadó-Anguera7, Aaron D Greenblatt4, Arthur E Jacobson8, Kenner C Rice8, Vicent Casadó7, Amy H Newman3, John W Winkelman5, Michael Michaelides2, Eric Weintraub4, Nora D Volkow9, Annabelle M Belcher4, Sergi Ferré1.   

Abstract

Identifying non-addictive opioid medications is a high priority in medical sciences, but μ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of μ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that μ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the μ-opioid-Gal1 receptor heteromer, exemplified by methadone.

Entities:  

Keywords:  Addiction; G-protein coupled receptors; Neuroscience; Therapeutics

Year:  2019        PMID： 30913037      PMCID： PMC6597217          DOI： 10.1172/JCI126912

Source DB:  PubMed          Journal:  J Clin Invest        ISSN： 0021-9738            Impact factor:   14.808


  65 in total

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Journal:  Pharmacol Rev       Date:  2014-02-10       Impact factor: 25.468

5.  Characterization of the cloned human mu opioid receptor.

Authors:  K Raynor; H Kong; A Mestek; L S Bye; M Tian; J Liu; L Yu; T Reisine
Journal:  J Pharmacol Exp Ther       Date:  1995-01       Impact factor: 4.030

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8.  Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies.

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  12 in total

1.  Opioid-galanin receptor heteromers differentiate the dopaminergic effects of morphine and methadone.

Authors:  Randal A Serafini; Venetia Zachariou
Journal:  J Clin Invest       Date:  2019-05-28       Impact factor: 14.808

2.  Preferential Gs protein coupling of the galanin Gal1 receptor in the µ-opioid-Gal1 receptor heterotetramer.

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6.  Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

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Review 9.  Consensus Guidelines on Rodent Models of Restless Legs Syndrome.

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Review 10.  Disrupting GPCR Complexes with Smart Drug-like Peptides.

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