Makoto Tominaga1 and David Julius2
1Department of Molecular Neurobiology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575 Japan
2Department of Cellular and Molecular Pharmacology, University of California, San Francisco,
513 Parnassus Avenue, San Francisco, California 94143-0450, USA
Abstract: Capsaicin, the main pungent ingredient in `hot' chili peppers, elicits burning pain by activating specific (vanilloid) receptors on sensory nerve endings. The cloned capsaicin receptor (VR1) is a nonselective cation channel with six transmembrane domains that is structurally related to a member of the TRP (transient receptor potential) channel family. VR1 is activated not only by capsaicin but also by increases in temperature that reach the noxious range (>43°C). Protons potentiate the effects of capsaicin or heat on VR1 activity by markedly decreasing the capsaicin concentration or temperature at which the channel is activated. Furthermore, a significant increase in proton concentration (pH <5.9) can evoke channel activity at room temperature. The analysis of single-channel currents in excised membrane patches suggests that capsaicin, heat or protons gate VR1 directly. VR1 can therefore be viewed as a molecular integrator of chemical and physical stimuli that elicit pain. VRL-1, a VR1 homologue, is not activated by vanilloids or protons, but can be activated by elevation in ambient temperature exceeding 52°C. These findings indicate that related ion channels may account for thermal responsiveness over a range of noxious temperature.
Keywords: Capsaicin receptor, Ion channel, Heat, Proton, Pain
Copyright© The Japanese Pharmacological Society 2000
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