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Modulation of TRP channels by resveratrol and other stilbenoids.

Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y - Mol Pain (2013)

Bottom Line: Otherwise, trans-stilbene showed no any effect on I AITC or I CAP.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.These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.

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.

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Resveratrol suppresses TRPA1 currents, but not TRPV1 currents in a concentration dependent manner in transfected HEK293 cells. A: Representative traces from whole-cell patch-clamp experiments show the IAITC (AITC, 100 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). B: Dose–response curve showing inhibition of IAITC by RES. Each point represents relative IAITC with different concentration of RES treatment normalized to the IAITC without RES treatment (mean ± SEM, n = 6–11). IC50 = 0.75 μM. C: Concentration curves of IAITC in the absence (open circles) and presence (filled circles) of RES. Note the maximum response was inhibited without changing the EC50 (61.2 μM for AITC, 61.7 μM for RES + AITC). D: Representative traces show the I2APB (2APB, 400 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). E: The bars graph shows RES significantly inhibits I2APB density (pA/pF). * p < 0.05, unpaired t – test. F: Representative traces show the ICAP (capsaicin, 20 nM) in the absence (left) or presence (right) of RES. G: Bars graph shows no effect of RES on ICAP. Numbers in parenthesis indicate cells tested. AITC or capsaicin was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.
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Figure 2: Resveratrol suppresses TRPA1 currents, but not TRPV1 currents in a concentration dependent manner in transfected HEK293 cells. A: Representative traces from whole-cell patch-clamp experiments show the IAITC (AITC, 100 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). B: Dose–response curve showing inhibition of IAITC by RES. Each point represents relative IAITC with different concentration of RES treatment normalized to the IAITC without RES treatment (mean ± SEM, n = 6–11). IC50 = 0.75 μM. C: Concentration curves of IAITC in the absence (open circles) and presence (filled circles) of RES. Note the maximum response was inhibited without changing the EC50 (61.2 μM for AITC, 61.7 μM for RES + AITC). D: Representative traces show the I2APB (2APB, 400 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). E: The bars graph shows RES significantly inhibits I2APB density (pA/pF). * p < 0.05, unpaired t – test. F: Representative traces show the ICAP (capsaicin, 20 nM) in the absence (left) or presence (right) of RES. G: Bars graph shows no effect of RES on ICAP. Numbers in parenthesis indicate cells tested. AITC or capsaicin was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.

Mentions: We examined the effects of resveratrol on the IAITC in HEK293 cells expressing mTRPA1. The AITC (100 μM) did not induce any significant current in untransfected HEK293 cells. In mTRPA1 expressing HEK293 cells, the IAITC (AITC, 100 μM) underwent a fast activation component and then by rapid inactivation (desensitization). After 3 min pretreatment of resveratrol (30 μM), not only was the time of the activation component clearly extended, but the magnitude of IAITC was significantly suppressed (Figure 2A). The inhibition of IAITC by resveratrol appeared from a low concentration (0.3 μM) with an IC50 value of approximately 0.75 μM (Figure 2B).


Modulation of TRP channels by resveratrol and other stilbenoids.

Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y - Mol Pain (2013)

Resveratrol suppresses TRPA1 currents, but not TRPV1 currents in a concentration dependent manner in transfected HEK293 cells. A: Representative traces from whole-cell patch-clamp experiments show the IAITC (AITC, 100 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). B: Dose–response curve showing inhibition of IAITC by RES. Each point represents relative IAITC with different concentration of RES treatment normalized to the IAITC without RES treatment (mean ± SEM, n = 6–11). IC50 = 0.75 μM. C: Concentration curves of IAITC in the absence (open circles) and presence (filled circles) of RES. Note the maximum response was inhibited without changing the EC50 (61.2 μM for AITC, 61.7 μM for RES + AITC). D: Representative traces show the I2APB (2APB, 400 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). E: The bars graph shows RES significantly inhibits I2APB density (pA/pF). * p < 0.05, unpaired t – test. F: Representative traces show the ICAP (capsaicin, 20 nM) in the absence (left) or presence (right) of RES. G: Bars graph shows no effect of RES on ICAP. Numbers in parenthesis indicate cells tested. AITC or capsaicin was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585750&req=5

Figure 2: Resveratrol suppresses TRPA1 currents, but not TRPV1 currents in a concentration dependent manner in transfected HEK293 cells. A: Representative traces from whole-cell patch-clamp experiments show the IAITC (AITC, 100 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). B: Dose–response curve showing inhibition of IAITC by RES. Each point represents relative IAITC with different concentration of RES treatment normalized to the IAITC without RES treatment (mean ± SEM, n = 6–11). IC50 = 0.75 μM. C: Concentration curves of IAITC in the absence (open circles) and presence (filled circles) of RES. Note the maximum response was inhibited without changing the EC50 (61.2 μM for AITC, 61.7 μM for RES + AITC). D: Representative traces show the I2APB (2APB, 400 μM) in the absence (left) or presence (right) of resveratrol (RES, 30 μM). E: The bars graph shows RES significantly inhibits I2APB density (pA/pF). * p < 0.05, unpaired t – test. F: Representative traces show the ICAP (capsaicin, 20 nM) in the absence (left) or presence (right) of RES. G: Bars graph shows no effect of RES on ICAP. Numbers in parenthesis indicate cells tested. AITC or capsaicin was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.
Mentions: We examined the effects of resveratrol on the IAITC in HEK293 cells expressing mTRPA1. The AITC (100 μM) did not induce any significant current in untransfected HEK293 cells. In mTRPA1 expressing HEK293 cells, the IAITC (AITC, 100 μM) underwent a fast activation component and then by rapid inactivation (desensitization). After 3 min pretreatment of resveratrol (30 μM), not only was the time of the activation component clearly extended, but the magnitude of IAITC was significantly suppressed (Figure 2A). The inhibition of IAITC by resveratrol appeared from a low concentration (0.3 μM) with an IC50 value of approximately 0.75 μM (Figure 2B).

Bottom Line: Otherwise, trans-stilbene showed no any effect on I AITC or I CAP.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.These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan.

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.

Show MeSH
Related in: MedlinePlus