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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 IAITC in DRG neurons. A, B: Representative traces show IAITC in the absence (A) or presence (B) of resveratrol (RES, 30 μM). C: Resveratrol significantly inhibits IAITC (pA). Numbers in parenthesis indicate cells tested. * p < 0.05, unpaired t - test. AITC was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.
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Figure 3: Resveratrol suppresses IAITC in DRG neurons. A, B: Representative traces show IAITC in the absence (A) or presence (B) of resveratrol (RES, 30 μM). C: Resveratrol significantly inhibits IAITC (pA). Numbers in parenthesis indicate cells tested. * p < 0.05, unpaired t - test. AITC was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.

Mentions: Because cell types differ in their membrane composition, we asked whether resveratrol would also suppress TRPA1 channels in sensory neurons. We then tested the effect of resveratrol on IAITC in rat DRG neurons. AITC, as a potent activator of TRPA1, has been used in patch-clamp experiments to detect the TRPA1 current. A previous study indicated that while there are AITC-sensitive cells in TRPA1 knockout mice, these are not where the TRPA1 is expressed. To confirm the IAITC in the DRG is a TRPA1-mediated event, capsaicin at 1 μM was applied at the end of recording using the patch-clamp preparation (see Methods section). We observed that AITC at 300 μM induced a large inward current in DRG neurons (Figure 3A). After treatment with resveratrol at 30 μM for 3 min, IAITC were strongly suppressed (Figure 3B, C) (−1228.8 ± 270.9 pA, n=5 for AITC without resveratrol treatment, vs -127.7 ± 20.8 pA, n = 5 for AITC with resveratrol treatment, p < 0.05). We confirmed that application of resveratrol alone at 30 μM caused no change of membrane currents in DRG neurons. Together, these data indicate that resveratrol suppress IAITC both in a heterologous expression system and in sensory neurons.


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 IAITC in DRG neurons. A, B: Representative traces show IAITC in the absence (A) or presence (B) of resveratrol (RES, 30 μM). C: Resveratrol significantly inhibits IAITC (pA). Numbers in parenthesis indicate cells tested. * p < 0.05, unpaired t - test. AITC 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 3: Resveratrol suppresses IAITC in DRG neurons. A, B: Representative traces show IAITC in the absence (A) or presence (B) of resveratrol (RES, 30 μM). C: Resveratrol significantly inhibits IAITC (pA). Numbers in parenthesis indicate cells tested. * p < 0.05, unpaired t - test. AITC was perfused until current reaching the peak. Holding potential (Vh) = −60 mV in all experiments.
Mentions: Because cell types differ in their membrane composition, we asked whether resveratrol would also suppress TRPA1 channels in sensory neurons. We then tested the effect of resveratrol on IAITC in rat DRG neurons. AITC, as a potent activator of TRPA1, has been used in patch-clamp experiments to detect the TRPA1 current. A previous study indicated that while there are AITC-sensitive cells in TRPA1 knockout mice, these are not where the TRPA1 is expressed. To confirm the IAITC in the DRG is a TRPA1-mediated event, capsaicin at 1 μM was applied at the end of recording using the patch-clamp preparation (see Methods section). We observed that AITC at 300 μM induced a large inward current in DRG neurons (Figure 3A). After treatment with resveratrol at 30 μM for 3 min, IAITC were strongly suppressed (Figure 3B, C) (−1228.8 ± 270.9 pA, n=5 for AITC without resveratrol treatment, vs -127.7 ± 20.8 pA, n = 5 for AITC with resveratrol treatment, p < 0.05). We confirmed that application of resveratrol alone at 30 μM caused no change of membrane currents in DRG neurons. Together, these data indicate that resveratrol suppress IAITC both in a heterologous expression system and in sensory neurons.

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