Abstract Title:

Pharmacological effects of cannabinoids on the Caco-2 cell culture model of intestinal permeability.

Abstract Source:

J Pharmacol Exp Ther. 2010 Jun 30. Epub 2010 Jun 30. PMID: 20592049

Abstract Author(s):

A Alhamoruni, A C Lee, K L Wright, M Larvin, S E O'Sullivan

Article Affiliation:

1 University of Nottingham;

Abstract:

Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. However, the effects of cannabinoids on intestinal permeability have not yet been established. The aim of the present study is to examine the effects of cannabinoids on intestinal permeability in an in vitro model. Caco-2 cells were grown until fully confluent on inserts in 12-well plates. Transepithelial electrical resistance (TEER) measurements were made as a measure of permeability. 50 muM ethylenediaminetetraacetic acid (EDTA) was applied to reversibly increase permeability (reduce TEER). The effects of cannabinoids on permeability in combination with EDTA, or alone, were assessed. Potential target sites of action were investigated using antagonists of the CB(1) receptor, CB(2) receptor, TRPV1, PPARgamma, PPARalpha, and a proposed cannabinoid receptor. When applied to the apical or basolateral membrane of Caco-2 cells, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) enhanced the speed of recovery of EDTA-induced increased permeability. This effect was sensitive to cannabinoid CB(1) receptor antagonism only. Apical application of endocannabinoids caused increased permeability, sensitive to cannabinoid CB(1) receptor antagonism. By contrast, when endocannabinoids were applied basolaterally, they enhanced the recovery of EDTA-induced increased permeability, and this involved additional activation of TRPV1. All cannabinoids tested increased the mRNA of the tight junction protein ZO-1, but only endocannabinoids also decreased the mRNA of Claudin-1. These findings suggest that endocannabinoids may play a role in modulating intestinal permeability and that plant derived cannabinoids such as THC and CBD may have therapeutic potential in conditions associated with abnormally permeable intestinal epithelium.

Study Type : In Vitro Study

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