Makoto Tominaga1 and David Julius2
1Departmentﾊof Molecular Neurobiology, Institute of Basic
Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575 Japan
2Departmentﾊ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ﾊ<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ｩ The Japanese Pharmacological Society 2000
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