title: Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion.
abstract: Here we describe a novel mechanism for plasma membrane insertion of the delta opioid receptor (DOR). In small dorsal root ganglion neurons, only low levels of DORs are present on the cell surface, in contrast to high levels of intracellular DORs mainly associated with vesicles containing calcitonin gene-related peptide (CGRP). Activation of surface DORs caused Ca(2+) release from IP(3)-sensitive stores and Ca(2+) entry, resulting in a slow and long-lasting exocytosis, DOR insertion, and CGRP release. In contrast, membrane depolarization or activation of vanilloid and P2Y(1) receptors induced a rapid DOR insertion. Thus, DOR activation induces a Ca(2+)-dependent insertion of DORs that is coupled to a release of excitatory neuropeptides, suggesting that treatment of inflammatory pain should include blockade of DORs.
authors.affiliation: Laboratory of Sensory System, Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
authors.forename: Shan-Xue
authors.initials: SX
authors.lastname: Jin
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wang
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Xu
authors.forename: Fang-Xiong
authors.initials: FX
authors.lastname: Zhang
authors.forename: Lie-Chen
authors.initials: LC
authors.lastname: Wang
authors.forename: Feng-Shou
authors.initials: FS
authors.lastname: Ning
authors.forename: Hai-Jiang
authors.initials: HJ
authors.lastname: Cai
authors.forename: Ji-Song
authors.initials: JS
authors.lastname: Guan
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Xiao
authors.forename: Zhi-Qing D
authors.initials: ZQ
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: He
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016716:PC12 Cells; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D009479:Neuropeptides; C546383:P2ry1 protein, mouse; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D017465:Receptors, Opioid, delta; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium