Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Pharmacol Exp Ther
2010 May 01;3332:547-54. doi: 10.1124/jpet.109.162594.
Show Gene links
Show Anatomy links
The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes.
Yang KH
,
Galadari S
,
Isaev D
,
Petroianu G
,
Shippenberg TS
,
Oz M
.
???displayArticle.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.
Ahrens,
The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
2009, Pubmed
Ahrens,
The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function.
2009,
Pubmed
Barann,
Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site.
2002,
Pubmed
Bisogno,
Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide.
2001,
Pubmed
Dascal,
The use of Xenopus oocytes for the study of ion channels.
1987,
Pubmed
,
Xenbase
De Petrocellis,
Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.
2008,
Pubmed
Drysdale,
Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells.
2006,
Pubmed
Engleman,
The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy.
2008,
Pubmed
Faerber,
The neuronal 5-HT3 receptor network after 20 years of research--evolving concepts in management of pain and inflammation.
2007,
Pubmed
Fan,
Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons.
1995,
Pubmed
Godlewski,
Cannabinoid receptor-independent inhibition by cannabinoid agonists of the peripheral 5-HT3 receptor-mediated von Bezold-Jarisch reflex.
2003,
Pubmed
Hejazi,
Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors.
2006,
Pubmed
,
Xenbase
Izzo,
Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.
2009,
Pubmed
Járai,
Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors.
1999,
Pubmed
Kathmann,
Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors.
2006,
Pubmed
Kwiatkowska,
A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).
2004,
Pubmed
Martin,
Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain.
2004,
Pubmed
Mechoulam,
Cannabidiol--recent advances.
2007,
Pubmed
Onaran,
Allosteric coupling and conformational fluctuations in proteins.
2009,
Pubmed
Oz,
Direct noncompetitive inhibition of 5-HT(3) receptor-mediated responses by forskolin and steroids.
2002,
Pubmed
,
Xenbase
Oz,
Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5-HT3 receptor-mediated responses in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Oz,
Cocaine inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Oz,
The solubilizing detergents, Tween 80 and Triton X-100 non-competitively inhibit alpha 7-nicotinic acetylcholine receptor function in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Oz,
Differential effects of endogenous and synthetic cannabinoids on alpha7-nicotinic acetylcholine receptor-mediated responses in Xenopus Oocytes.
2004,
Pubmed
,
Xenbase
Oz,
Functional coupling of human L-type Ca2+ channels and angiotensin AT1A receptors coexpressed in xenopus laevis oocytes: involvement of the carboxyl-terminal Ca2+ sensors.
1998,
Pubmed
,
Xenbase
Oz,
Receptor-independent actions of cannabinoids on cell membranes: focus on endocannabinoids.
2006,
Pubmed
Oz,
The endogenous cannabinoid anandamide inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus oocytes.
2007,
Pubmed
,
Xenbase
Parker,
Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.
2002,
Pubmed
Parker,
Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).
2004,
Pubmed
Pertwee,
Emerging strategies for exploiting cannabinoid receptor agonists as medicines.
2009,
Pubmed
Przegaliński,
WIN 55,212-2-induced reduction of cocaine hyperlocomotion: possible inhibition of 5-HT(3) receptor function.
2005,
Pubmed
Qin,
TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons.
2008,
Pubmed
Riering,
Analgesic effects of 5-HT3 receptor antagonists.
2004,
Pubmed
Ross,
Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol.
2008,
Pubmed
Russo,
Agonistic properties of cannabidiol at 5-HT1a receptors.
2005,
Pubmed
Ryan,
Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia.
2006,
Pubmed
Rácz,
Anandamide effects on 5-HT(3) receptors in vivo.
2008,
Pubmed
Scuderi,
Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.
2009,
Pubmed
Slatkin,
Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis.
2007,
Pubmed
Spivak,
The endocannabinoid anandamide inhibits the function of alpha4beta2 nicotinic acetylcholine receptors.
2007,
Pubmed
Thompson,
The 5-HT3 receptor as a therapeutic target.
2007,
Pubmed
Tramèr,
Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.
2001,
Pubmed
Varvel,
Interactions between THC and cannabidiol in mouse models of cannabinoid activity.
2006,
Pubmed
Xiong,
Anandamide inhibition of 5-HT3A receptors varies with receptor density and desensitization.
2008,
Pubmed
,
Xenbase
Yakel,
5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line.
1988,
Pubmed
Zhang,
Volatile general anaesthetic actions on recombinant nACh alpha 7, 5-HT3 and chimeric nACh alpha 7-5-HT3 receptors expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
