Christie MacDonald J
Pain Management Research Institute, Kolling Institute, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Br J Pharmacol. 2006 Jun;148(4):385-6. doi: 10.1038/sj.bjp.0706756. Epub 2006 May 8.
mu-Opioid (MOP) and cannabinoid CB1 receptors mediate overlapping pharmacological responses in clinically important areas such as drug abuse and pain management, and functional interactions between agonists at these receptors have long been recognized. In the present issue of this Journal, Rios and co-workers have provided the first strong evidence that the two receptors interact directly when coexpressed in the same cells. The authors report a close physical association between MOP and CB1 receptors and novel pharmacological interactions of MOP and CB1 agonists. They argue that MOP/CB1 heterodimer formation explains these interactions. If correct, the direct interaction of MOP and CB1 pharmacophores in a quaternary complex would provide real benefits by opening the potential for development of novel MOP/CB1 small molecules or new strategies for use of current ligands. However, a lot more evidence will be required before the heterodimer interpretation can be accepted. If it turns out that MOP and CB1 receptors do not readily form hetero-oligomers, the study by Rios and co-workers shows that they are still friends but there may be few benefits.
μ阿片受体（MOP）和大麻素CB1受体在药物滥用和疼痛管理等临床重要领域介导重叠的药理反应，并且这些受体激动剂之间的功能相互作用早已为人所知。在本期杂志中，里奥斯及其同事提供了首个有力证据，表明这两种受体在同一细胞中共表达时会直接相互作用。作者报告了MOP与CB1受体之间紧密的物理关联以及MOP和CB1激动剂的新型药理相互作用。他们认为MOP/CB1异二聚体的形成解释了这些相互作用。如果正确的话，MOP和CB1药效基团在四级复合物中的直接相互作用将通过开启开发新型MOP/CB1小分子或使用现有配体的新策略的可能性而带来实际益处。然而，在异二聚体解释被接受之前还需要更多的证据。如果结果表明MOP和CB1受体不容易形成异源寡聚体，那么里奥斯及其同事的研究表明它们仍然是“朋友”，但可能益处不大。
