Effects of cannabidiol on the function of 伪₇-nicotinic acetylcholine receptors

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• 作者：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
• 关键词：ACh ; acetylcholine ; ANOVA ; analysis of variance ; BAPTA ; 1 ; 2-bis (o-aminophenoxy) ethane-N ; N ; N&prime ; N&prime ; -tetraacetic acid ; DMSO ; dimethyl sulfoxide ; HEPES ; 4-(2-hydroxyethyl) piperazineethane sulfonic acid ; MBS ; modified Barth's solution ; PTX ; pertussis toxin.
• 刊名：European Journal of Pharmacology
• 出版年：15 November, 2013
• 年：2013
• 卷：720
• 期：1-3
• 页码：310-319
• 全文大小：680 K

文摘

The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned 伪₇ subunit of the human nicotinic acetylcholine (伪₇ nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 渭M)-induced currents with an IC₅₀ value of 11.3 碌M. Other phytocannabinoids such as cannabinol and 螖⁹-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-纬-S binding to the membranes of oocytes injected with 伪₇ nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 碌M) did not affect the activity of endogenous Ca²⁺-dependent Cl^{鈭?/sup> channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca2+ 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] 伪-bungarotoxin was not inhibited by CBD (10 碌M) 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 伪₇-receptor induced currents were also recoded. Bath application of CBD (10 碌M) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [3H] norepinephrine release evoked by nicotine (30 碌M) was also inhibited by 10 碌M CBD. Our results indicate that CBD inhibits the function of the 伪₇-nACh receptor.}