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The Journal of Neuroscience, July 9, 2003, 23(14):6058-6062

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BRIEF COMMUNICATION
Possible Involvement of P2Y₂ Metabotropic Receptors in ATP-Induced Transient Receptor Potential Vanilloid Receptor 1-Mediated Thermal Hypersensitivity

Tomoko Moriyama,¹ Tohko Iida,^1,2 Kimiko Kobayashi,³ Tomohiro Higashi,¹ Tetsuo Fukuoka,³ Hideki Tsumura,⁴ Catherine Leon,⁵ Noboru Suzuki,⁴ Kazuhide Inoue,^6,7 Christian Gachet,⁵ Koichi Noguchi,³ and Makoto Tominaga¹

¹Department of Cellular and Molecular Physiology, Mie University School of Medicine, Tsu, Mie 514-8507, Japan, ²Inoue Foundation for Science, Tokyo 150-0033, Japan, ³Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663-8501, Japan, ⁴Institute of Laboratory Animals, Mie University, Tsu, Mie 514-8507, ⁵Institut National de la Santé et de la Recherche Médicale Unité 311, 67065 Strasbourg, France, ⁶Division of Biosignaling, National Institute of Health Sciences, Tokyo 158-8501, and ⁷Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan

The capsaicin receptor transient receptor potential V1 (TRPV1; also known as vanilloid receptor 1) is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been reported that extracellular ATP potentiates the TRPV1 currents evoked by capsaicin or protons and reduces the temperature threshold for its activation through metabotropic P2Y receptors in a PKC-dependent pathway, suggesting that TRPV1 activation could trigger the sensation of pain at normal body temperature in the presence of ATP. Here, we show that ATP-induced thermal hyperalgesia was abolished in mice lacking TRPV1, suggesting the functional interaction between ATP and TRPV1 at a behavioral level. However, thermal hyperalgesia was preserved in P2Y₁ receptor-deficient mice. Patch-clamp analyses using mouse dorsal root ganglion neurons indicated the involvement of P2Y₂ rather than P2Y₁ receptors. Coexpression of TRPV1 mRNA with P2Y₂ mRNA, but not P2Y₁ mRNA, was determined in the rat lumbar DRG using in situ hybridization histochemistry. These data indicate the importance of metabotropic P2Y₂ receptors in nociception through TRPV1.

Key words: pain; thermal hyperalgesia; capsaicin receptor; P2Y receptor; ATP; UTP

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Received Feb. 5, 2003; revised Apr. 29, 2003; accepted May. 2, 2003.

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