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


METHODS
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).


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.


CONCLUSIONS
CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. aaizzo@unina.it
Angelo A
AA
Izzo
Raffaele
R
Capasso
Gabriella
G
Aviello
Francesca
F
Borrelli
Barbara
B
Romano
Fabiana
F
Piscitelli
Laura
L
Gallo
Francesco
F
Capasso
Pierangelo
P
Orlando
Vincenzo
V
Di Marzo
D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002186:Cannabinoids / Q000627:therapeutic use*; D002188:Cannabis / Q000737:chemistry*; D004386:Duodenum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D063388:Endocannabinoids; D004983:Ethanolamines; D005765:Gastrointestinal Agents / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007079:Ileitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D010169:Palmitic Acids / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000577:Amides; D001095:Arachidonic Acids; D002186:Cannabinoids; C571431:Cnr2 protein, mouse; D063388:Endocannabinoids; D004983:Ethanolamines; D005765:Gastrointestinal Agents; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C005958:palmidrol; C010695:cannabichromene; C078814:anandamide