Decreased enteric fatty acid amide hydrolase activity is associated with colonic inertia in slow transit constipation.
BACKGROUND
Constipation is one of the most common chronic digestive complaints. Gastrointestinal transit studies have divided it into three patterns: normal transit, slow transit constipation (STC), and outlet obstruction. It has been demonstrated that STC patients respond poorly to standard therapies, and the etiology of STC remains poorly understood. Animal studies have also shown that fatty acid amide hydrolase (FAAH) controls intestinal motility through its putative receptors or non-receptor-mediated pathways. However, the role of FAAH in STC has not been elaborated.


METHODS
A case series was carried out on thirty-two STC patients fulfilling the Rome II criteria and on 24 controls. All of the subjects underwent a laparotomy in Shengjing Hospital. Colonic specimens were obtained and used for FAAH expression analysis, enzyme activity assay, and cannabinoid detection.


RESULTS
FAAH immunoreactivity occurred in the enteric neurons and in the surface epithelial and glands. The expression level and enzyme activity of FAAH in the STC group were both significantly lower than those in the control group (P < 0.05). The amounts of anandamide, 2-arachidonylglycerol, and palmitoylethanolamide, which are negatively correlated with enzyme activity, were significantly higher in the constipation group than that in the control group. In the STC group, cannabinoid receptor type 1 immunoreactivity occurred predominantly in the submucosal and myenteric fibers that were obviously strong and wave-like in their appearance. Enteric ganglions decreased or disappeared.


CONCLUSIONS
The tone of the enteric cannabinoids system is disturbed in STC, and the decreased enteric FAAH activity contributes to colonic inertia in STC.
Department of Pediatric Surgery, Major Laboratory of Chinese Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, Shenyang, China.
Shu-Cheng
SC
Zhang
Wei-Lin
WL
Wang
Peng-Jun
PJ
Su
Kai-Lei
KL
Jiang
Zheng-Wei
ZW
Yuan
D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism* / Q000502:physiology*; D002648:Child; D003248:Constipation / Q000145:classification / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005772:Gastrointestinal Transit / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism / Q000502:physiology; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C571130:CNR1 protein, human
clinical gastroenterology in the elderly; colonic motility and disorders; enteric neural pathways; functional disorders.