The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3A Receptor-Mediated Currents in Xenopus laevis Oocytes

Authors

Keun-Hang Susan Yang, Chapman UniversityFollow
Sehamuddin Galadari, UAE University, Al Ain, Abu Dhabi, UAE
Dmytro Isaev, UAE University, Al Ain, Abu Dhabi, UAE
Georg Petroianu, UAE University, Al Ain, Abu Dhabi, UAE
Toni S. Shippenberg, National Institutes of HealthFollow
Murat Oz, National Institutes of HealthFollow

Document Type

Article

Publication Date

2010

Abstract

The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 receptors. Neither intracellular BAPTA injection nor pertussis toxin pretreatment (5 μg/ml) altered the CBD-evoked inhibition of 5-HT-induced currents. CBD inhibition was inversely correlated with 5-HT3A expression levels and mean 5-HT3 receptor current density. Pretreatment with actinomycin D, which inhibits protein transcription, decreased the mean 5-HT3 receptor current density and increased the magnitude of CBD inhibition. These data demonstrate that CBD is an allosteric inhibitor of 5-HT3 receptors expressed in X. laevis oocytes. They further suggest that allosteric inhibition of 5-HT3 receptors by CBD may contribute to its physiological roles in the modulation of nociception and emesis.

Comments

This article was originally published in Journal of Pharmacology and Experimental Therapeutics , volume 333, issue 2, in 2010. DOI: 0.1124/jpet.109.162594

Recommended Citation

Yang, Keun-Hang, et al. "The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes." Journal of Pharmacology and Experimental Therapeutics 333.2 (2010): 547-554.
doi: 0.1124/jpet.109.162594

Peer Reviewed

1

Copyright

U.S. Government work not protected by U.S. copyright