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

Angelo A Izzo, Raffaele Capasso, Gabriella Aviello, Francesca Borrelli, Barbara Romano, Fabiana Piscitelli, Laura Gallo, Francesco Capasso, Pierangelo Orlando, Vincenzo Di Marzo

Research output: Contribution to journalArticle

69 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1444-1460
Number of pages17
JournalBritish Journal of Pharmacology
Volume166
Issue number4
Early online date17 May 2012
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Ankyrins
Cannabinoids
Cannabis
Endocannabinoids
Inflammation
Croton Oil
Cannabinoid Receptors
Gastrointestinal Motility
Electric Stimulation
Gastrointestinal Transit
cannabichromene
Baths
Ileum
Liquid Chromatography
Small Intestine
Mass Spectrometry
Up-Regulation
Down-Regulation
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Animals
  • Arachidonic Acids
  • Cannabinoids
  • Cannabis
  • Duodenum
  • Endocannabinoids
  • Ethanolamines
  • Gastrointestinal Agents
  • Gastrointestinal Motility
  • Gene Expression Regulation
  • Ileitis
  • Ileum
  • In Vitro Techniques
  • Jejunum
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Contraction
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Transient Receptor Potential Channels
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. / Izzo, Angelo A; Capasso, Raffaele; Aviello, Gabriella; Borrelli, Francesca; Romano, Barbara; Piscitelli, Fabiana; Gallo, Laura; Capasso, Francesco; Orlando, Pierangelo; Di Marzo, Vincenzo.

In: British Journal of Pharmacology, Vol. 166, No. 4, 06.2012, p. 1444-1460.

Research output: Contribution to journalArticle

Izzo, AA, Capasso, R, Aviello, G, Borrelli, F, Romano, B, Piscitelli, F, Gallo, L, Capasso, F, Orlando, P & Di Marzo, V 2012, 'Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice', British Journal of Pharmacology, vol. 166, no. 4, pp. 1444-1460. https://doi.org/10.1111/j.1476-5381.2012.01879.x
Izzo, Angelo A ; Capasso, Raffaele ; Aviello, Gabriella ; Borrelli, Francesca ; Romano, Barbara ; Piscitelli, Fabiana ; Gallo, Laura ; Capasso, Francesco ; Orlando, Pierangelo ; Di Marzo, Vincenzo. / Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. In: British Journal of Pharmacology. 2012 ; Vol. 166, No. 4. pp. 1444-1460.
@article{c8ee8a5f34e345cb864d5331f7826913,
title = "Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice",
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.",
keywords = "Animals, Arachidonic Acids, Cannabinoids, Cannabis, Duodenum, Endocannabinoids, Ethanolamines, Gastrointestinal Agents, Gastrointestinal Motility, Gene Expression Regulation, Ileitis, Ileum, In Vitro Techniques, Jejunum, Male, Mice, Mice, Inbred ICR, Muscle Contraction, Palmitic Acids, Polyunsaturated Alkamides, RNA, Messenger, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Transient Receptor Potential Channels, Journal Article, Research Support, Non-U.S. Gov't",
author = "Izzo, {Angelo A} and Raffaele Capasso and Gabriella Aviello and Francesca Borrelli and Barbara Romano and Fabiana Piscitelli and Laura Gallo and Francesco Capasso and Pierangelo Orlando and {Di Marzo}, Vincenzo",
note = "{\circledC} 2012 The Authors. British Journal of Pharmacology {\circledC} 2012 The British Pharmacological Society.",
year = "2012",
month = "6",
doi = "10.1111/j.1476-5381.2012.01879.x",
language = "English",
volume = "166",
pages = "1444--1460",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice

AU - Izzo, Angelo A

AU - Capasso, Raffaele

AU - Aviello, Gabriella

AU - Borrelli, Francesca

AU - Romano, Barbara

AU - Piscitelli, Fabiana

AU - Gallo, Laura

AU - Capasso, Francesco

AU - Orlando, Pierangelo

AU - Di Marzo, Vincenzo

N1 - © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

KW - Animals

KW - Arachidonic Acids

KW - Cannabinoids

KW - Cannabis

KW - Duodenum

KW - Endocannabinoids

KW - Ethanolamines

KW - Gastrointestinal Agents

KW - Gastrointestinal Motility

KW - Gene Expression Regulation

KW - Ileitis

KW - Ileum

KW - In Vitro Techniques

KW - Jejunum

KW - Male

KW - Mice

KW - Mice, Inbred ICR

KW - Muscle Contraction

KW - Palmitic Acids

KW - Polyunsaturated Alkamides

KW - RNA, Messenger

KW - Receptor, Cannabinoid, CB1

KW - Receptor, Cannabinoid, CB2

KW - Transient Receptor Potential Channels

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1476-5381.2012.01879.x

DO - 10.1111/j.1476-5381.2012.01879.x

M3 - Article

C2 - 22300105

VL - 166

SP - 1444

EP - 1460

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -