Hydroxy-alpha-sanshool activates TRPV1 and TRPA1 in sensory neurons.
Sanshools are major active ingredients of Zanthoxylum piperitum and are used as food additives in East Asia. Sanshools cause irritant, tingling and sometimes paresthetic sensations on the tongue. However, the molecular mechanism underlying the pungent or tingling sensation induced by sanshools is not known. Because many transient receptor potential (TRP) channels are responsible for the sensations induced by various spices and food additives, we expressed 17 TRP channels in human embryonic kidney (HEK) cells and investigated their activation by hydroxy-alpha-sanshool (HalphaSS) or hydroxy-beta-sanshool (HbetaSS) isolated from Zanthoxylum piperitum. It was found that HalphaSS, but not HbetaSS, depolarized sensory neurons with concomitant firing of action potentials and evoked inward currents. Among 17 TRP channels expressed in HEK cells, HalphaSS caused Ca(2+) influx in cells transfected with TRPV1 or TRPA1, and evoked robust inward currents in cells transfected with TRPV1 or TRPA1. In primary cultured sensory neurons, HalphaSS induced inward currents and Ca(2+) influx in a capsazepine-dependent manner. Moreover, HalphaSS-induced currents and Ca(2+) influx were greatly diminished in TRPV1(-/-) mice. HalphaSS evoked licking behavior when injected into a single hind paw of wild-type mice, but this was much reduced in TRPV1-deficient mice. These results indicate that TRPV1 and TRPA1 are molecular targets of HalphaSS in sensory neurons. We conclude that the activations of TRPV1 and TRPA1 by HalphaSS explain its unique pungent, tingling sensation.
Koo
Jae Yeon
JY
The Sensory Research Center, Creative Research Initiatives, Seoul National University, College of Pharmacy, Gwanak, Shinlim-9 Dong Seoul, 151-742, Korea.
Jang
Yongwoo
Y
Cho
Hawon
H
Lee
Chang-Hun
CH
Jang
Kyoung Hwa
KH
Chang
Yong Ha
YH
Shin
Jongheon
J
Oh
Uhtaek
U
D000577:Amides / Q000032:analysis / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*; D013649:Taste / Q000187:drug effects / Q000502:physiology; D014162:Transfection / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
D000577:Amides; D010936:Plant Extracts; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; C100574:sanshool; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium