Mu and delta receptors: their role in analgesia in the differential effects of opioid peptides on analgesia.
Mu and delta receptors: their role in analgesia in the differential effects of opioid peptides on analgesia.
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Mu 和 δ 受体：它们在阿片肽对镇痛的不同作用的镇痛中的作用。
DOI：
10.1016/0024-3205(82)90558-6
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发表时间：
1982
期刊：
影响因子：
6.1
通讯作者：
Westfall,TC
中科院分区：
文献类型：
--
作者：
Vaught,JL;Rothman,RB;Westfall,TC
通过小鼠甩尾实验，各种阿片类药物（icv）的镇痛效价排序为β h 2-内啡肽> D-Ala 2-D-Leu 5脑啡肽>吗啡> D-Ala 2-氨基脑啡肽⪢氨基脑啡肽⪢leu-脑啡肽。假设mu受体介导镇痛，那么mu受体亲和力与镇痛效力之间有时明显缺乏相关性（即：D-Ala 2-D-Leu 5-脑啡肽对mu受体的亲和力是吗啡的17倍，但作为镇痛剂的效力是吗啡的18倍）。此外，亚镇痛剂量的各种阿片肽对镇痛反应有相反的作用。leu -脑啡肽、D-Ala 2-D-Leu 5-脑啡肽或β - h-内啡肽能增强吗啡或D-Ala 2-氨基脑啡肽的镇痛作用，而metenkephalin或D-Ala 2-氨基脑啡肽能拮抗阿片类药物引起的镇痛作用。以脑啡肽为原型配体（选择性为100倍），基于其镇痛作用，我们认为，亮氨酸-脑啡肽样肽与受体相互作用，作为“激动剂”促进和满足脑啡肽样肽作为“拮抗剂”，以减轻镇痛。鉴于mu和delta受体之间偶联的生化证据，我们认为脑啡肽促进或减弱镇痛的机制是这种偶联的直接体内结果。此外，各种阿片配体的镇痛效力可能与它们同时占据mu和delta受体的组合有更好的相关性。
Utilizing the mouse tail-flick assay, the rank order of analgesic potency for various opioids (icv) is β h 2-endorphin> D-Ala 2-D-Leu 5 eenkephalin> morphine> D-Ala 2-met-enkephalinamide⪢ met-enkephalin⪢ leu-enkephalin. Assuming mu receptor mediation of analgesia, there is an obvious lack of correlation at times between mu receptor affinity and analgesic potency (ie: D-Ala 2-D-Leu 5-enkephalin has 1 7 the affinity of morphine for the mu receptor but is 18X more potent as an analgesic). Additionally, sub-analgesic doses of various opioid peptides have opposite effects on analgesic responses. Leu-enkephalin, D-Ala 2-D-Leu 5-enkephalin or β h-endorphin potentiate morphine or D-Ala 2-met-enkephalinamide analgesia whereas metenkephalin or D-Ala 2-met-enkephalinamide antagonize opioid-induced analgesia. Using the enkephalins as the prototypic delta ligands (100 fold selective) and based on their effects on analgesia, we suggest that leu-enkephalin-like peptides interact with the delta receptor as an “agonist” to facilitate and met-enkephalin-like peptides as an “antagonist” to attenuate analgesia. Given the biochemical evidence of a coupling between mu and delta receptors, we suggest that the mechanism of facilitation or attenuation of analgesia by the enkephalins is a direct in vivo consequence of this coupling. Further, the analgesic potencies of various opioid ligands can be better correlated to the combination of their simultaneous occupancy of mu and delta receptors.