Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 12 - Trang 6951-6956 - 2001
Makoto Tominaga1, Makoto Wada1, Masayuki Masu1
1Department of Molecular Neurobiology, Institute of Basic Medical Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan; and Department of Physiology, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan

Tóm tắt

The capsaicin (vanilloid) receptor, VR1, is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been proposed that ATP, released from different cell types, initiates the sensation of pain by acting predominantly on nociceptive ionotropic purinoceptors located on sensory nerve terminals. In this study, we examined the effects of extracellular ATP on VR1. In cells expressing VR1, ATP increased the currents evoked by capsaicin or protons through activation of metabotropic P2Y 1 receptors in a protein kinase C-dependent pathway. The involvement of G q/11 -coupled metabotropic receptors in the potentiation of VR1 response was confirmed in cells expressing both VR1 and M1 muscarinic acetylcholine receptors. In the presence of ATP, the temperature threshold for VR1 activation was reduced from 42°C to 35°C, such that normally nonpainful thermal stimuli (i.e., normal body temperature) were capable of activating VR1. This represents a novel mechanism through which the large amounts of ATP released from damaged cells in response to tissue trauma might trigger the sensation of pain.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 12

6951-6956

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