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

被引:131
作者
Izzo, Angelo A. [1 ]
Capasso, Raffaele [1 ]
Aviello, Gabriella [1 ]
Borrelli, Francesca [1 ]
Romano, Barbara [1 ]
Piscitelli, Fabiana [2 ]
Gallo, Laura [2 ]
Capasso, Francesco [1 ]
Orlando, Pierangelo [3 ]
Di Marzo, Vincenzo [2 ]
机构
[1] Univ Naples Federico II, Dept Expt Pharmacol, I-80131 Naples, Italy
[2] CNR, Inst Biomol Chem, Endocannabinoid Res Grp, I-80078 Pozzuoli, NA, Italy
[3] CNR, Inst Prot Biochem, I-80078 Pozzuoli, NA, Italy
关键词
2-arachydonoylglycerol; anandamide; cannabichromene; cannabinoids; cannabinoid receptors; gastrointestinal transit; ileum; intestinal motility; transient receptor potential (TRP) channels; TRPA1; DELTA-OPIOID-RECEPTOR; POTENTIAL ANKYRIN 1; PIG SMALL-INTESTINE; GASTROINTESTINAL MOTILITY; EXPERIMENTAL COLITIS; MOUSE INTESTINE; BOWEL-DISEASE; CB1; RECEPTORS; TRP CHANNELS; NITRIC-OXIDE;
D O I
10.1111/j.1476-5381.2012.01879.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1444 / 1460
页数:17
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