内体
伤害感受器
受体
兴奋剂
内生
内吞作用
类阿片
化学
细胞生物学
医学
伤害
神经科学
生物
内科学
作者
Nestor N. Jiménez-Vargas,Jing Gong,Matthew Wisdom,Dane D. Jensen,Rocco Latorre,Alan Hégron,Shavonne Teng,Jesse J. DiCello,Pradeep Rajasekhar,Nicholas A. Veldhuis,Simona Carbone,Yang Yu,Cintya López-López,Josue Jaramillo-Polanco,Meritxell Canals,David E. Reed,Alan Lomax,Brian L. Schmidt,Kam W. Leong,Stephen Vanner
标识
DOI:10.1073/pnas.2000500117
摘要
Significance G protein-coupled receptors are considered to function principally at the cell surface. We present evidence that the δ-opioid receptor (DOPr) signals from endosomes to cause a sustained inhibition of pain. Opioids from the inflamed human and mouse colon, along with selective agonists that evoked DOPr internalization, inhibited the excitability of nociceptors by a mechanism requiring DOPr endocytosis. DOPr in endosomes generated a subset of signals in subcellular compartments that inhibited neuronal excitability. A DOPr agonist that was encapsulated into nanoparticles designed to selectively activate DOPr in endosomes of nociceptors caused a long-lasting inhibition of neuronal excitability and pain. Our results support the hypothesis that endosomal signaling of DOPr is an endogenous mechanism and therapeutic target for relief from inflammatory pain.
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