Alhamoruni, A. and Lee, A. C. and Wright, K. L. and Larvin, M. and O'Sullivan, S. E. (2010) Pharmacological effects of cannabinoids on the Caco-2 cell culture model of intestinal permeability. Journal of Pharmacology and Experimental Therapeutics, 335 (1). pp. 92-102. ISSN 0022-3565Full text not available from this repository.
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. EDTA (50 μM) 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 cannabinoid (CB)1 receptor, CB2 receptor, transient receptor potential vanilloid subtype 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)γ, PPARα, and a proposed cannabinoid receptor. When applied to the apical or basolateral membrane of Caco-2 cells, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) enhanced the speed of recovery of EDTA-induced increased permeability. This effect was sensitive to cannabinoid CB1 receptor antagonism only. Apical application of endocannabinoids caused increased permeability, sensitive to cannabinoid CB1 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 zona occludens-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.
|Journal or Publication Title:||Journal of Pharmacology and Experimental Therapeutics|
|Subjects:||R Medicine > RM Therapeutics. Pharmacology|
|Departments:||Faculty of Health and Medicine > Biomedical & Life Sciences|
|Deposited By:||Mr Richard Ingham|
|Deposited On:||16 Jun 2011 09:21|
|Last Modified:||24 Feb 2017 05:00|
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