title: Opioid receptor desensitization: mechanisms and its link to tolerance.
abstract: Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor.
authors.affiliation: Laboratoire de Signalisation, Électrophysiologie et Imagerie des Lésions D'ischémie-Reperfusion Myocardique, Université de Caen, UPRES EA 4650, IFR 146 ICORE Caen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
authors.affiliation: Centre National de la Recherche Scientifique, ERL 3649 Paris, France ; Institut National de la Santé et de la Recherche Médicale, UMR-S 1124 Paris, France ; Université Paris Descartes, Neuroplasticité et Thérapies des Addictions Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.affiliation: Centre National de la Recherche Scientifique, ERL 3649 Paris, France ; Institut National de la Santé et de la Recherche Médicale, UMR-S 1124 Paris, France ; Université Paris Descartes, Neuroplasticité et Thérapies des Addictions Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marie
keywords: biased signaling; desensitization; opioid receptors; receptor trafficking; tolerance mechanisms