Neurobiology Laboratory and State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, PR China.
Neuropeptides. 2013 Apr;47(2):125-31. doi: 10.1016/j.npep.2012.10.008. Epub 2012 Dec 2.
The Mu opioid receptor (MOR) has been shown to participate in the analgesic effect of the calcitonin gene-related peptide (CGRP) in the nucleus accumbens (NAc) of adult rats. However, it is not clear whether and how CGRP regulates the MOR at the molecular levels. In the present study, it is found that the level of MORs on the cell membrane of NAc neurons was increased twice more than the control level following CGRP treatment (1μM, 30min), which is a phenomenon that was blocked by the peptidergic antagonist CGRP8-37. No direct physical interaction was observed between MORs and CGRP receptors, and neither brefeldin A nor dynosore preincubation affected such effects of CGRP. However, addition of 20μM monensin 1h before CGRP treatment significantly blocked the action of CGRP on surface MORs. In living animals, microinjection of CGRP (1nmol in 1μl) into the NAc partially restored morphine antinociception in morphine-tolerant rats, and the effect of CGRP on surface MORs extended beyond normal NAc neurons to chronic morphine-treated NAc neurons. To conclude, these results demonstrate that CGRP can act on MORs and increase the number of surface MORs in NAc neurons, partially explaining the involvement of opioid receptors in CGRP-induced antinociception in the rat NAc.
促钙素基因相关肽（CGRP）通过伏核（NAc）中的μ阿片受体（MOR）参与成年大鼠的镇痛作用。然而，尚不清楚 CGRP 是否以及如何在分子水平上调节 MOR。本研究发现，CGRP（1μM，30min）处理后，NAc 神经元细胞膜上的 MOR 水平增加了两倍以上，这一现象被 CGRP 肽拮抗剂 CGRP8-37 阻断。MOR 与 CGRP 受体之间没有观察到直接的物理相互作用，布雷非德菌素 A 或 dynosore 预孵育也不会影响 CGRP 的这种作用。然而，在 CGRP 处理前 1 小时加入 20μM 莫能菌素可显著阻断 CGRP 对表面 MOR 的作用。在活体动物中，将 CGRP（1nmol 在 1μl 中）微注射到 NAc 中可部分恢复吗啡耐受大鼠的吗啡镇痛作用，并且 CGRP 对表面 MOR 的作用不仅局限于正常的 NAc 神经元，还扩展到慢性吗啡处理的 NAc 神经元。总之，这些结果表明，CGRP 可以作用于 MOR 并增加 NAc 神经元表面 MOR 的数量，部分解释了阿片受体参与 CGRP 诱导的大鼠 NAc 镇痛作用。
