Marie Nicolas, Jauzac Philippe, Allouche Stéphane
Laboratoire de Pharmacologie Moléculaire de la Tolérance aux Opiacés, Centre Hospitalier et Universitaire de Caen, Université de Caen, France.
Ann Med Interne (Paris). 2003 Nov;154 Spec No 2:S73-80.
Despite side effects which appear upon chronic administration of opioid agonists, these drugs remain widely used and effective for pain relief. Among these side effects, tolerance is the major factor limiting the effectiveness of these drugs. Desensitization, defined by a decrease of opioid receptor transduction, would be a crucial step in the development of tolerance. Molecular mechanisms of opioid receptor desensitization have been extensively studied on cellular models and have been found to involve various proteins and different steps such as receptor phosphorylation, internalization, and recycling or degradation into intracellular compartments. In the present review, we discuss the role of opioid receptor internalization and sorting in desensitization and tolerance processes.
尽管长期使用阿片类激动剂会出现副作用，但这些药物仍被广泛使用且对缓解疼痛有效。在这些副作用中，耐受性是限制这些药物有效性的主要因素。脱敏作用，定义为阿片受体转导的降低，将是耐受性发展的关键步骤。阿片受体脱敏的分子机制已在细胞模型上进行了广泛研究，发现涉及多种蛋白质和不同步骤，如受体磷酸化、内化、再循环或降解到细胞内区室。在本综述中，我们讨论了阿片受体内化和分选在脱敏和耐受过程中的作用。
