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This Article Full Text Full Text (PDF) All Versions of this Article: 576/3/809    most recent jphysiol.2006.112250v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohta, T. Articles by Ito, S. Search for Related Content PubMed PubMed Citation Articles by Ohta, T. Articles by Ito, S. Related Collections Neuroscience

¹ Laboratory of Pharmacology, Department of Biochemical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
² Biological Chemistry, Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan

5-Hydroxytryptamine (5-HT) is one of the major chemical mediators released in injured and inflamed tissue and is capable of inducing hyperalgesia in vivo. However, the cellular mechanisms of 5-HT-induced hyperalgesia remain unclear. Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive receptors. In the present study, we determined whether 5-HT changes TRPV1 functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal rats, using Ca²⁺ imaging and whole-cell patch-clamp techniques. In more than 70% of DRG neurons, 5-HT potentiated the increases of [Ca²⁺]_i induced by capsaicin, protons and noxious heat. Capsaicin-induced current and depolarizing responses, and proton-induced currents were also augmented by 5-HT. RT-PCR analysis revealed the expression of 5-HT_2A and 5-HT₇ receptors in rat DRG neurons. Agonists for 5-HT_2A and 5-HT₇ receptors mimicked the potentiating effect of 5-HT, and their antagonists decreased it. In DRG ipsilateral to the complete Freund's adjuvant-injected inflammation side, expression levels of 5-HT_2A and 5-HT₇ mRNAs increased, and the potentiating effect of 5-HT was more prominent than in the contralateral control side. These results suggest that the PKC- and PKA-mediated signalling pathways are involved in the potentiating effect of 5-HT on TRPV1 functions through the activation of 5-HT_2A and 5-HT₇ receptors, respectively. Under inflammatory conditions, the increases of the biosynthesis of these 5-HT receptors may lead to further potentiation of TRPV1 functions, resulting in the generation of inflammatory hyperalgesia in vivo.

(Received 26 April 2006; accepted after revision 10 August 2006; first published online 10 August 2006)
Corresponding author T. Ohta: Laboratory of Pharmacology, Department of Biochemical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Email: tohta{at}vetmed.hokudai.ac.jp

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				T. Ohta, T. Imagawa, and S. Ito Novel Gating and Sensitizing Mechanism of Capsaicin Receptor (TRPV1): TONIC INHIBITORY REGULATION OF EXTRACELLULAR SODIUM THROUGH THE EXTERNAL PROTONATION SITES ON TRPV1 J. Biol. Chem., April 4, 2008; 283(14): 9377 - 9387. [Abstract] [Full Text] [PDF]