Gong J, Strong J A, Zhang S, Yue X, DeHaven R N, Daubert J D, Cassel J A, Yu G, Mansson E, Yu L
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, OH 45267-0521, USA.
FEBS Lett. 1998 Nov 13;439(1-2):152-6. doi: 10.1016/s0014-5793(98)01362-3.
Endomorphins were recently identified as endogenous ligands with high selectivity for mu opioid receptors. We have characterized the ability of endomorphins to bind to and functionally activate the cloned human mu opioid receptor. Both endomorphin-1 and endomorphin-2 exhibited binding selectivity for the mu opioid receptor over the delta and kappa opioid receptors. Both agonists inhibited forskolin-stimulated increase of cAMP in a dose-dependent fashion. When the mu opioid receptor was coexpressed in Xenopus oocytes with G protein-activated K+ channels, application of either endomorphin activated an inward K+ current. This activation was dose-dependent and blocked by naloxone. Both endomorphins acted as full agonists with efficacy similar to that of [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO). These data indicate that endomorphins act as full agonists at the human mu opioid receptor, capable of stimulating the receptor to inhibit the cAMP/adenylyl cyclase pathway and activate G-protein-activated inwardly rectifying potassium (GIRK) channels.
内吗啡肽最近被鉴定为对μ阿片受体具有高选择性的内源性配体。我们已经对内吗啡肽与克隆的人μ阿片受体结合并在功能上激活该受体的能力进行了表征。内吗啡肽-1和内吗啡肽-2对μ阿片受体的结合选择性均高于δ和κ阿片受体。两种激动剂均以剂量依赖性方式抑制福斯高林刺激的cAMP增加。当μ阿片受体与G蛋白激活的K⁺通道在非洲爪蟾卵母细胞中共表达时，施加任何一种内吗啡肽均可激活内向K⁺电流。这种激活是剂量依赖性的，并被纳洛酮阻断。两种内吗啡肽均作为完全激动剂，其效力与[D-丙氨酸²，N-甲基苯丙氨酸⁴，甘氨酸-醇⁵]脑啡肽（DAMGO）相似。这些数据表明，内吗啡肽在人μ阿片受体上作为完全激动剂起作用，能够刺激该受体抑制cAMP/腺苷酸环化酶途径并激活G蛋白激活的内向整流钾（GIRK）通道。
