The Journal of clinical investigation · 2019
Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cai Ning-Sheng, Quiroz César, Bonaventura Jordi, Bonifazi Alessandro, Cole Thomas O, Purks Julia, Billing Amy S, Massey Ebonie, Wagner Michael, Wish Eric D, Guitart Xavier, Rea William, Lam Sherry, Moreno Estefanía, Casadó-Anguera Verònica, Greenblatt Aaron D, Jacobson Arthur E, Rice Kenner C, Casadó Vicent, Newman Amy H, Winkelman John W, Michaelides Michael, Weintraub Eric, Volkow Nora D, Belcher Annabelle M, Ferré Sergi
Аннотация
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.