title: Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors.
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 Δ(9)-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 Ca(2+)-dependent Cl(-) channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing 2mM Ba(2+). Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [(125)I] 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, [(3)H] 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.
authors.affiliation: Laboratory of Functional Lipidomics, Department of Pharmacology, College of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, United Arab Emirates.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mahgoub
authors.forename: Susan Yang
authors.initials: SY
authors.lastname: Keun-Hang
authors.forename: Vadym
authors.initials: V
authors.lastname: Sydorenko
authors.forename: Abrar
authors.initials: A
authors.lastname: Ashoor
authors.forename: Nadine
authors.initials: N
authors.lastname: Kabbani
authors.forename: Lina
authors.initials: L
authors.lastname: Al Kury
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Howarth
authors.forename: Dmytro
authors.initials: D
authors.lastname: Isaev
authors.forename: Sehamuddin
authors.initials: S
authors.lastname: Galadari
authors.forename: Murat
authors.initials: M
authors.lastname: Oz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002038:Bungarotoxins; D018733:Nicotinic Antagonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002185:Cannabidiol; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009538:Nicotine; D002794:Choline; D000109:Acetylcholine; D009638:Norepinephrine
keywords: 1,2-bis (o-aminophenoxy) ethane-N, N,N′,N′-tetraacetic acid; 4-(2-hydroxyethyl) piperazineethane sulfonic acid; ACh; ANOVA; BAPTA; Cannabidiol; Cannabinoids; DMSO; HEPES; MBS; Nicotinic receptors; PTX; Xenopus oocyte; acetylcholine; analysis of variance; dimethyl sulfoxide; modified Barth's solution; pertussis toxin.