Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice

Authors

  • Angelo A Izzo,

    Corresponding author
    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
      Angelo A Izzo, Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. E-mail: aaizzo@unina.it and Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli (NA), Italy. E-mail: vdimarzo@icmib.na.cnr.it
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  • Raffaele Capasso,

    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Gabriella Aviello,

    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Francesca Borrelli,

    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Barbara Romano,

    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Fabiana Piscitelli,

    1. Institute of Biomolecular Chemistry, National Research Council, Pozzuoli (NA), Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Laura Gallo,

    1. Institute of Biomolecular Chemistry, National Research Council, Pozzuoli (NA), Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Francesco Capasso,

    1. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
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  • Pierangelo Orlando,

    1. Institute of Protein Biochemistry, National Research Council, Pozzuoli (NA), Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
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  • Vincenzo Di Marzo

    Corresponding author
    1. Institute of Biomolecular Chemistry, National Research Council, Pozzuoli (NA), Italy
    2. Endocannabinoid Research Group, Pozzuoli (NA), Italy
      Angelo A Izzo, Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. E-mail: aaizzo@unina.it and Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli (NA), Italy. E-mail: vdimarzo@icmib.na.cnr.it
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Angelo A Izzo, Department of Experimental Pharmacology, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. E-mail: aaizzo@unina.it and Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei, 34, Comprensorio Olivetti, 80078, Pozzuoli (NA), Italy. E-mail: vdimarzo@icmib.na.cnr.it

Abstract

BACKGROUND AND PURPOSE Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states.

EXPERIMENTAL APPROACH Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2-arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT-PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS).

KEY RESULTS Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB1 receptors and down-regulation of CB2 receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil-induced hypermotility. In vitro, CBC reduced preferentially EFS- versus ACh-induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists.

CONCLUSION AND IMPLICATIONS CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.

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