title: Modulation of TRP channels by resveratrol and other stilbenoids.
abstract: BACKGROUND
  Resveratrol (3,5,4' - trihydroxy-trans-stilbene), a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo.
  
  
  RESULTS
  We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC)-induced currents (I AITC) in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG) neurons. Instead, pinosylvin methyl ether (PME), another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (I CAP) in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the I CAP, and PME had no effect on the I AITC. Otherwise, trans-stilbene showed no any effect on I AITC or I CAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one.
  
  
  CONCLUSIONS
  These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.
authors: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.
authors: Lina
authors: L
authors: Yu
authors: Shenglan
authors: S
authors: Wang
authors: Yoko
authors: Y
authors: Kogure
authors: Satoshi
authors: S
authors: Yamamoto
authors: Koichi
authors: K
authors: Noguchi
authors: Yi
authors: Y
authors: Dai
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051379:Mice; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D000094162:Phytoalexins
chemical_list: D002211:Capsaicin; D017879:Isothiocyanates; D000077185:Resveratrol; D013267:Stilbenes; D050051:Transient Receptor Potential Channels; C049032:pinosylvin; D000094162:Phytoalexins; C004471:allyl isothiocyanate