Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons

NEUROPHARMACOLOGY

卷:55

Article

Tang, He-Bin¹  Li, Yu-Sang²  Miyano, Kanako¹  Nakata, Yoshihiro¹ 

[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pharmacol, Minami Ku, Hiroshima 7348553, Japan

[2] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pathol, Minami Ku, Hiroshima 7348551, Japan

关键词: Dorsal root ganglion neuron;    Neurokinin-1 receptor;    Phosphorylation of transient receptor potential vanilloid receptor subtype 1;    Substance P release;   

DOI  :  10.1016/j.neuropharm.2008.08.037

来源: Elsevier

【 摘 要 】

The present Study was conducted to determine whether the activation of neurokinin-1 receptor (NK-1R) by its agonist (GR73632) enhances the capsaicin-evoked Substance P (SP) release using a radioimmunoassay. A pre-exposure to GR73632 enhanced the capsaicin-evoked SP release in a time- and dose-dependent manner. The augmentation of capsaicin-evoked SP release by GR73632 was completely inhibited by pharmacological blockade of NK-1R or transient receptor potential vanilloid receptor subtype I (TRPV1), and was partially attenuated by the inhibition of either protein kinase C (PKC), cyclooxygenase (COX) or phospholipase C (PLC), p38 or p42/44 mitogen-activated protein (MAP) kinase, but not protein kinase A. This augmentation of SP release was further increased by inhibition of c-Jun NH2-terminal kinase. A short-term (10 min) exposure to GR73632 resulted in an increase in the TRPV1 phosphorylation. The increase in the TRPV1 phosphorylated forms induced by a 60-min exposure to GR73632 was completely abolished by the inhibition of either PKC, COX or PLC, p38 or p42/44 MAP kinases. Immunocytochemistry study demonstrated that the NK-1R and TRPV1 were mainly co-expressed in the small-sized neurons. These findings suggest that the activation of NK-1R by its agonist, by sensitizing the TRPV1 through the PKC phosphorylation of TRPV1, may play a role in the enhancement of the capsaicin-evoked SP release from Cultured rat DRG neurons. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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