Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors

Mohamed Mahgoub, Susan Yang Keun-Hang, Vadym Sydorenko, Abrar Ashoor, Nadine Kabbani, Lina Al Kury, Bassem Sadek, Christopher F. Howarth, Dmytro Isaev, Sehamuddin Galadari, Murat Oz

Research output: Contribution to journalArticle

Abstract

The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 μM)-induced currents with an IC50 value of 11.3 μM. Other phytocannabinoids such as cannabinol and Δ9-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-γ-S binding to the membranes of oocytes injected with α7 nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 μM) did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca 2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [ 125I] α-bungarotoxin was not inhibited by CBD (10 μM) in oocytes membranes. Using whole cell patch clamp technique in CA1 stratum radiatum interneurons of rat hippocampal slices, currents induced by choline, a selective-agonist of α7-receptor induced currents were also recoded. Bath application of CBD (10 μM) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [ 3H] norepinephrine release evoked by nicotine (30 μM) was also inhibited by 10 μM CBD. Our results indicate that CBD inhibits the function of the α7-nACh receptor.

Original languageEnglish (US)
Pages (from-to)310-319
Number of pages10
JournalEuropean Journal of Pharmacology
Volume720
Issue number1-3
DOIs
StatePublished - Nov 15 2013

Keywords

  • Cannabidiol
  • Cannabinoids
  • Nicotinic receptors
  • Xenopus oocyte

ASJC Scopus subject areas

  • Pharmacology

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    Mahgoub, M., Keun-Hang, S. Y., Sydorenko, V., Ashoor, A., Kabbani, N., Al Kury, L., Sadek, B., Howarth, C. F., Isaev, D., Galadari, S., & Oz, M. (2013). Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors. European Journal of Pharmacology, 720(1-3), 310-319. https://doi.org/10.1016/j.ejphar.2013.10.011