Functional independence of endogenous μ- and δ-opioid receptors co-expressed in cholinergic interneurons

eLife

Emily J Platt¹  David Farrens¹  James Carroll²  Seksiri Arttamangkul³ 

[1] Department of Chemical Physiology and Biochemistry, School of Medicine, Oregon Health & Science University, Portland, United States;Program in Biomedical Sciences, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, United States;The Vollum Institute, Oregon Health & Science University, Portland, United States;

关键词: cholinergic interneurons;    opioid receptors;    co-localization;    desensitization;    internalization;    dimerization;    Mouse;   

DOI  :  10.7554/eLife.69740

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Class A G-protein-coupled receptors (GPCRs) normally function as monomers, although evidence from heterologous expression systems suggests that they may sometimes form homodimers and/or heterodimers. This study aims to evaluate possible functional interplay of endogenous µ- and δ-opioid receptors (MORs and DORs) in mouse neurons. Detecting GPCR dimers in native tissues, however, has been challenging. Previously, MORs and DORs co-expressed in transfected cells have been reported to form heterodimers, and their possible co-localization in neurons has been studied in knock-in mice expressing genetically engineered receptors fused to fluorescent proteins. Here, we find that single cholinergic neurons in the mouse striatum endogenously express both MORs and DORs. The receptors on neurons from live brain slices were fluorescently labeled with a ligand-directed labeling reagent, NAI-A594. The selective activation of MORs and DORs, with DAMGO (µ-agonist) and deltorphin (δ-agonist) inhibited spontaneous firing in all cells examined. In the continued presence of agonist, the firing rate returned to baseline as the result of receptor desensitization with the application of deltorphin but was less observed with the application of DAMGO. In addition, agonist-induced internalization of DORs but not MORs was detected. When MORs and DORs were activated simultaneously with [Met5]-enkephalin, desensitization of MORs was facilitated but internalization was not increased. Together, these results indicate that while MORs and DORs are expressed in single striatal cholinergic interneurons, the two receptors function independently.

【 授权许可】

CC BY