Gut 2006;55:1373-1376; doi:10.1136/gut.2005.090472
Copyright © 2006 BMJ Publishing Group Ltd & British Society of Gastroenterology
LEADING ARTICLE
Endocannabinoid overactivity and intestinal inflammation
V Di Marzo1, A A Izzo2
1 Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Napoli, Italy
2 Department of Experimental Pharmacology, University of Naples "Federico II", Naples, Italy
Correspondence to:
Correspondence to:
Dr V Di Marzo
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy;vdimarzo@icmib.na.cnr.it
Cannabinoid receptors of type 1 and 2 (CB1 and CB2), endogenous ligands that activate them (endocannabinoids), and mechanisms for endocannabinoid biosynthesis and inactivation have been identified in the gastrointestinal system. Activation of CB1 receptors by endocannabinoids produces relaxation of the lower oesophageal sphincter and inhibition of gastric acid secretion, intestinal motility, and fluid stimulated secretion. However, stimulation of cannabinoid receptors impacts on gastrointestinal functions in several other ways. Recent data indicate that the endocannabinoid system in the small intestine and colon becomes over stimulated during inflammation in both animal models and human inflammatory disorders. The pathological significance of this "endocannabinoid overactivity" and its possible exploitation for therapeutic purposes are discussed here.
Abbreviations: 2-AG, 2-arachidonoylglycerol; CB1 and CB2, cannabinoid receptors of type 1 and 2; DNBS, dinitrobenzene sulphonic acid; FAAH, fatty acid amide hydrolase; IBD, inflammatory bowel diseases; LPS, lipopolysaccharide; TNF-
, tumour necrosis factor ; TRPV1, transient receptor potential vanilloid type 1 channel
Keywords: cannabinoid; inflammatory bowel disease; vanilloid; colitis; intestinal inflammation