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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Pharmacological Effects of Cannabinoids on the Caco-2 Cell Culture Model of Intestinal Permeability

A. Alhamoruni, A. C. Lee, K. L. Wright, M. Larvin and S. E. O'Sullivan
Journal of Pharmacology and Experimental Therapeutics October 2010, 335 (1) 92-102; DOI: https://doi.org/10.1124/jpet.110.168237
A. Alhamoruni
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A. C. Lee
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K. L. Wright
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M. Larvin
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S. E. O'Sullivan
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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. 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.

Footnotes

  • A.A. was supported by a scholarship from the Department of Higher Education of Libya .

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.168237.

  • ABBREVIATIONS:

    THC
    Δ9-tetrahydrocannabinol
    CBD
    cannabidiol
    CB
    cannabinoid
    AEA
    anandamide
    2-AG
    2-arachidonoyl glycerol
    TRPV1
    transient receptor potential vanilloid subtype 1
    PPAR
    peroxisome proliferator-activated receptor
    TJ
    tight junction
    TEER
    transepithelial electrical resistance
    PBS
    phosphate-buffered saline
    FD
    fluorescent dextran
    AM251
    N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
    GW9662
    2-chloro-5-nitro-N-phenylbenzamide
    GW6471
    [(2S)-2-[[(1Z)-1-methyl-3-oxo-3-[4-(trifluoromethyl)phenyl]-1-propenyl]amino]-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propyl]-carbamic acid ethyl ester
    O-1918
    1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]benzene
    ZO-1
    zona occludens-1
    ANOVA
    analysis of variance
    CP 55,940
    (1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol
    AM630
    6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone.

  • Received March 19, 2010.
  • Accepted June 29, 2010.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Pharmacological Effects of Cannabinoids on the Caco-2 Cell Culture Model of Intestinal Permeability

A. Alhamoruni, A. C. Lee, K. L. Wright, M. Larvin and S. E. O'Sullivan
Journal of Pharmacology and Experimental Therapeutics October 1, 2010, 335 (1) 92-102; DOI: https://doi.org/10.1124/jpet.110.168237

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Pharmacological Effects of Cannabinoids on the Caco-2 Cell Culture Model of Intestinal Permeability

A. Alhamoruni, A. C. Lee, K. L. Wright, M. Larvin and S. E. O'Sullivan
Journal of Pharmacology and Experimental Therapeutics October 1, 2010, 335 (1) 92-102; DOI: https://doi.org/10.1124/jpet.110.168237
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