Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons

<p>Abstract</p> <p>Background</p> <p>Although substance P (SP) is an important primary afferent modulator in nociceptive processes, it is unclear whether SP regulates its own release from primary sensory neurons.</p> <p>Results</p> <p>Using a hig...

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Main Authors: Arihiro Koji, Li Yu-Sang, Tang He-Bin, Nakata Yoshihiro
Format: Article
Language:English
Published: SAGE Publishing 2007-12-01
Series:Molecular Pain
Online Access:http://www.molecularpain.com/content/3/1/42
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author Arihiro Koji
Li Yu-Sang
Tang He-Bin
Nakata Yoshihiro
author_facet Arihiro Koji
Li Yu-Sang
Tang He-Bin
Nakata Yoshihiro
author_sort Arihiro Koji
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Although substance P (SP) is an important primary afferent modulator in nociceptive processes, it is unclear whether SP regulates its own release from primary sensory neurons.</p> <p>Results</p> <p>Using a highly sensitive radioimmunoassay for SP, we have demonstrated that the activation of neurokinin-1 receptor by SP or GR73632 (a potent neurokinin-1 receptor agonist) triggered an increase of SP release from cultured adult rat dorsal root ganglion (DRG) neurons depending on the dose and exposure time within 60 min, and thereafter, the SP release level gradually decreased over 360 min. Accompanying the SP release, a significant reduction in the percentage of neurons expressing neurokinin-1 receptor on their membranes during exposure to SP (200 pg/dish) occurred time dependently (56 ± 5% and 32 ± 2% at 180 and 360 min, respectively). The GR73632-evoked (10 nM, 60 min) SP release was attenuated by several inhibitors for mitogen-activated protein kinase kinase, p38 mitogen-activated protein (MAP) kinase and cyclooxygenase-2 (COX-2), protein kinase C (PKC), respectively. In contrast, a c-Jun NH<sub>2</sub>-terminal kinase inhibitor increased the GR73632-evoked SP release.</p> <p>Conclusion</p> <p>These results indicate that the neurokinin-1 receptor activation by its agonists regulates the SP release process involving the activation of MAP kinases, PKCs and COX-2 from cultured DRG neurons.</p>
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spelling doaj.art-d08cc3e718fe43b8a814b6178c50e0602022-12-21T23:20:17ZengSAGE PublishingMolecular Pain1744-80692007-12-01314210.1186/1744-8069-3-42Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neuronsArihiro KojiLi Yu-SangTang He-BinNakata Yoshihiro<p>Abstract</p> <p>Background</p> <p>Although substance P (SP) is an important primary afferent modulator in nociceptive processes, it is unclear whether SP regulates its own release from primary sensory neurons.</p> <p>Results</p> <p>Using a highly sensitive radioimmunoassay for SP, we have demonstrated that the activation of neurokinin-1 receptor by SP or GR73632 (a potent neurokinin-1 receptor agonist) triggered an increase of SP release from cultured adult rat dorsal root ganglion (DRG) neurons depending on the dose and exposure time within 60 min, and thereafter, the SP release level gradually decreased over 360 min. Accompanying the SP release, a significant reduction in the percentage of neurons expressing neurokinin-1 receptor on their membranes during exposure to SP (200 pg/dish) occurred time dependently (56 ± 5% and 32 ± 2% at 180 and 360 min, respectively). The GR73632-evoked (10 nM, 60 min) SP release was attenuated by several inhibitors for mitogen-activated protein kinase kinase, p38 mitogen-activated protein (MAP) kinase and cyclooxygenase-2 (COX-2), protein kinase C (PKC), respectively. In contrast, a c-Jun NH<sub>2</sub>-terminal kinase inhibitor increased the GR73632-evoked SP release.</p> <p>Conclusion</p> <p>These results indicate that the neurokinin-1 receptor activation by its agonists regulates the SP release process involving the activation of MAP kinases, PKCs and COX-2 from cultured DRG neurons.</p>http://www.molecularpain.com/content/3/1/42
spellingShingle Arihiro Koji
Li Yu-Sang
Tang He-Bin
Nakata Yoshihiro
Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
Molecular Pain
title Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
title_full Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
title_fullStr Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
title_full_unstemmed Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
title_short Activation of the neurokinin-1 receptor by substance P triggers the release of substance P from cultured adult rat dorsal root ganglion neurons
title_sort activation of the neurokinin 1 receptor by substance p triggers the release of substance p from cultured adult rat dorsal root ganglion neurons
url http://www.molecularpain.com/content/3/1/42
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AT liyusang activationoftheneurokinin1receptorbysubstanceptriggersthereleaseofsubstancepfromculturedadultratdorsalrootganglionneurons
AT tanghebin activationoftheneurokinin1receptorbysubstanceptriggersthereleaseofsubstancepfromculturedadultratdorsalrootganglionneurons
AT nakatayoshihiro activationoftheneurokinin1receptorbysubstanceptriggersthereleaseofsubstancepfromculturedadultratdorsalrootganglionneurons