Identification of a receptor for neuropeptide VGF and its role in neuropathic pain
| العنوان: | Identification of a receptor for neuropeptide VGF and its role in neuropathic pain |
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| المؤلفون: | Ya-Chun, Chen, Alessandro, Pristerá, Mahmood, Ayub, Richard S, Swanwick, Kersti, Karu, Yosuke, Hamada, Andrew S C, Rice, Kenji, Okuse |
| المصدر: | The Journal of Biological Chemistry |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Receptors, Neuropeptide, Neurons, Membrane Glycoproteins, Sensory Receptor Cells, Macrophages, Neuropeptides, Calcium Intracellular Release, Pain, VGF, Mass Spectrometry, Peptide Fragments, Rats, Receptors, Complement, Mice, Neuropeptide, Neurobiology, gC1qR, Animals, Humans, Neuralgia, Calcium, Sensory Neurons, Microglia, Neuropathic Pain |
| الوصف: | Background: VGF is a neuropeptide involved in chronic pain. Results: VGF-derived peptide TLQP-21 activates macrophages. We identified gC1qR as a receptor for TLQP-21. Conclusion: TLQP-21 and gC1qR are involved in chronic pain pathways. Significance: TLQP-21 and gC1qR may be drug targets for chronic pain treatment. VGF (nonacronymic) is a neuropeptide precursor that plays multiple roles in regulation of energy balance, reproduction, hippocampal synaptic plasticity, and pain. Data from a number of pain models showed significant up-regulation of VGF in sensory neurons. TLQP-21, one of the VGF-derived neuropeptides, has been shown to induce a hyperalgesic response when injected subcutaneously into the hind paw of mice. However, the precise role of VGF-derived neuropeptides in neuropathic pain and the molecular identity of the receptor for VGF-derived peptides are yet to be investigated. Here we identified gC1qR, the globular heads of the C1q receptor, as the receptor for TLQP-21 using chemical cross-linking combined with mass spectrometry analysis. TLQP-21 caused an increase in intracellular Ca2+ levels in rat macrophages and microglia. Inoculation of TLQP-21-stimulated macrophages into rat hind paw caused mechanical hypersensitivity. The increase in intracellular Ca2+ levels in macrophages was attenuated by either siRNA or neutralizing antibodies against gC1qR. Furthermore, application of the gC1qR-neutralizing antibody to rats with partial sciatic nerve ligation resulted in a delayed onset of nerve injury-associated mechanical hypersensitivity. These results indicate that gC1qR is the receptor for TLQP-21 and plays an important role in chronic pain through activation of macrophages. Because direct association between TLQP-21 and gC1qR is required for activation of macrophages and causes hypersensitivity, disrupting this interaction may be a useful new approach to develop novel analgesics. |
| تدمد: | 1083-351X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid________::f615f3df167d38ea14ecc610ec75ed95 https://pubmed.ncbi.nlm.nih.gov/24106277 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.pmid..........f615f3df167d38ea14ecc610ec75ed95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X |
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