Nerve growth factor facilitates metabotropic glutamate receptor agonist-induced calcium elevation in dorsal root ganglion neurons

[Speaker] Takayoshi Masuoka:1
[Co-author] Yuka Yamashita:1, Junko Yoshida:1, Masashi Tawa:1, Matomo Nishio:1, Takaharu Ishibashi:1
1:Department of Pharmacology, Kanazawa Medical University, Japan

Nerve growth factor (NGF), one of the neurotrophins, facilitates sensitivities to noxious stimuli in primary sensory neurons in inflammation. Although endogenous glutamate modulates pain reception mediated by metabotropic glutamate receptors 1 and 5 (mGluR1/5) in primary sensory afferents, it has not been clarified whether NGF signaling modulates mGluR1/5-mediate response. In this study, we examined the effect of NGF on mGluR1/5-mediated responses in cultured dorsal root ganglion (DRG) neurons.
Intracellular calcium concentration in control DRG neurons was scarcely changed under perfusion of DHPG, an mGluR1/5 agonist. On the other hand, treatment of NGF for 3 days markedly increased the proportion of neurons responding to DHPG (increase in calcium concentration), which was abolished in calcium free extracellular solution. In addition, DHPG-induced calcium current was blocked by 5'-iodoresiniferatoxin, a transient receptor potential V1 (TRPV1) antagonist, in NGF-treated DRG neurons. Therefore, the functional interaction between mGluR1/5 and TRPV1 seems to facilitate in NGF-treated DRG neurons. To evaluate underlying molecular mechanism, we examined the expression of mGluR1/5, TRPV1 and A-kinase anchoring protein 5 (AKAP5; the scaffolding protein). NGF increased expression of TRPV1 and AKAP5 protein, while expression of mGluR1 and mGluR5 protein showed no significant change. Immunoprecipitation experiments showed that TRPV1-AKAP5 complex and phosphorylation of TRPV1 at S800 increase by the treatment of NGF, while amount of mGluR1/5-TRPV1 complex remained unchanged.
These results suggest that NGF sensitizes mGluR1/5-mediate response in primary sensory neurons possibly through increase in TRPV1 and/or the phosphorylation.
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