Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion.
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.
Bao
Lan
L
Laboratory of Sensory System, Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jin
Shan-Xue
SX
Zhang
Chen
C
Wang
Li-Hua
LH
Xu
Zhen-Zhong
ZZ
Zhang
Fang-Xiong
FX
Wang
Lie-Chen
LC
Ning
Feng-Shou
FS
Cai
Hai-Jiang
HJ
Guan
Ji-Song
JS
Xiao
Hua-Sheng
HS
Xu
Zhi-Qing D
ZQ
He
Cheng
C
Hökfelt
Tomas
T
Zhou
Zhuan
Z
Zhang
Xu
X
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
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