The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes.

Article Details

Citation

Copy to clipboard

Yang KH, Galadari S, Isaev D, Petroianu G, Shippenberg TS, Oz M

The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes.

J Pharmacol Exp Ther. 2010 May;333(2):547-54. doi: 10.1124/jpet.109.162594. Epub 2010 Feb 16.

PubMed ID

20160007 [ View in PubMed

]

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 microM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 microM). CBD (1 microM) 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 microM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 microM, 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 microg/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.

DrugBank Data that Cites this Article

Drugs

Cannabidiol

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cannabidiol	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Antagonist	Details