RT Journal Article
SR Electronic
T1 Curcumin Acts as a Positive Allosteric Modulator of <em>α</em><sub>7</sub>-Nicotinic Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory Pain
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 190
OP 200
DO 10.1124/jpet.117.245068
VO 365
IS 1
A1 Eslam Gaber El Nebrisi
A1 Deniz Bagdas
A1 Wisam Toma
A1 Halima Al Samri
A1 Anna Brodzik
A1 Yasmin Alkhlaif
A1 Keun-Hang Susan Yang
A1 Frank Christopher Howarth
A1 Imad M. Damaj
A1 Murat Oz
YR 2018
UL http://jpet.aspetjournals.org/content/365/1/190.abstract
AB Effects of curcumin, a major ingredient of turmeric, were tested on the function of the α7-subunit of the human nicotinic acetylcholine (α7-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 μM) with an EC50 value of 0.2 µM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca2+-dependent Cl− 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 [125I]α-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 α7-nACh receptors. Curcumin potentiated the antinociceptive effects of the α7-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 α7-nACh receptor and reverses nociception in mouse models of tonic and visceral pain.