Abstract
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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.