Curcumin acts as a positive allosteric modulator of a 7 -nicotinic acetylcholine receptors and_ reverses nociception in mouse models of inflammatory pain

Eslam Gaber El Nebrisi, Deniz Bagdas, Wisam Toma, Halima Al Samri, Anna Brodzik, Yasmin Alkhlaif, Keun Hang Susan Yang, Frank Christopher Howarth, Imad M. Damaj, O. Z. Murat

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume365
Issue number1
DOIs
Publication statusPublished - Apr 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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