TY - JOUR
T1 - Curcumin acts as a positive allosteric modulator of a 7 -nicotinic acetylcholine receptors and_ reverses nociception in mouse models of inflammatory pain
AU - Nebrisi, Eslam Gaber El
AU - Bagdas, Deniz
AU - Toma, Wisam
AU - Samri, Halima Al
AU - Brodzik, Anna
AU - Alkhlaif, Yasmin
AU - Yang, Keun Hang Susan
AU - Howarth, Frank Christopher
AU - Damaj, Imad M.
AU - Murat, O. Z.
N1 - Funding Information:
The research in this study was supported by grants from National Cancer Institute [CA206028] to I.M.D. and from CMHS, UAE University to M.O. We gratefully acknowledge Dr. Jon Lindstrom (University of Pennsylvania) for providing cDNA clones of the human a7-nACh receptor subunit, and Dr. Isabel Bermudez-Diaz (Oxford Brookes University) for human a2, a3, a4, b2, and b4 subunits.
Funding Information:
The research in this study was supported by grants from National Cancer Institute [CA206028] to I.M.D. and from CMHS, UAE University to M.O. 1E.G.E.N. and D.B. contributed equally to this paper. http://.doi.org/10.1124/jpet.117.245068. s This article has supplemental material available at jpet.aspetjournals.org.
Publisher Copyright:
Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics
PY - 2018/4
Y1 - 2018/4
N2 - Effects of curcumin, a major ingredient of turmeric, were tested on the function of the a 7 -subunit of the human nicotinic acetylcholine (a 7 -nACh) receptor expressed in Xenopus oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of currents induced by acetylcholine (ACh; 100 mM) with an EC 50 value of 0.2 mM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca 21 dependent Cl 2 channels expressed endogenously in oocytes. Importantly, the extent of curcumin potentiation was enhanced significantly by decreasing ACh concentrations. Curcumin did not alter specific binding of [ 125 I]a-bungarotoxin. In addition, curcumin attenuated nociceptive behavior in both tonic and visceral pain models without affecting motor and locomotor activity and without producing tolerance. Pharmacological and genetic approaches revealed that the antinociceptive effect of curcumin was mediated by a 7 -nACh receptors. Curcumin potentiated the antinociceptive effects of the a 7 -nACh receptor agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU282987). Collectively, our results indicate that curcumin is a positive allosteric modulator of a 7 -nACh receptor and reverses nociception in mouse models of tonic and visceral pain.
AB - Effects of curcumin, a major ingredient of turmeric, were tested on the function of the a 7 -subunit of the human nicotinic acetylcholine (a 7 -nACh) receptor expressed in Xenopus oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of currents induced by acetylcholine (ACh; 100 mM) with an EC 50 value of 0.2 mM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca 21 dependent Cl 2 channels expressed endogenously in oocytes. Importantly, the extent of curcumin potentiation was enhanced significantly by decreasing ACh concentrations. Curcumin did not alter specific binding of [ 125 I]a-bungarotoxin. In addition, curcumin attenuated nociceptive behavior in both tonic and visceral pain models without affecting motor and locomotor activity and without producing tolerance. Pharmacological and genetic approaches revealed that the antinociceptive effect of curcumin was mediated by a 7 -nACh receptors. Curcumin potentiated the antinociceptive effects of the a 7 -nACh receptor agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU282987). Collectively, our results indicate that curcumin is a positive allosteric modulator of a 7 -nACh receptor and reverses nociception in mouse models of tonic and visceral pain.
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U2 - 10.1124/jpet.117.245068
DO - 10.1124/jpet.117.245068
M3 - Article
C2 - 29339457
AN - SCOPUS:85045847763
SN - 0022-3565
VL - 365
SP - 190
EP - 200
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -