Abnormal anandamide metabolism in celiac disease.
The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.
Department of Biomedical Sciences, University of Teramo, Teramo, Italy. nbattista@unite.it
Natalia
N
Battista
Antonio
A
Di Sabatino
Monia
M
Di Tommaso
Paolo
P
Biancheri
Cinzia
C
Rapino
Francesca
F
Vidali
Cinzia
C
Papadia
Chiara
C
Montana
Alessandra
A
Pasini
Alberto
A
Lanzini
Vincenzo
V
Villanacci
Gino R
GR
Corazza
Mauro
M
Maccarrone
D000328:Adult; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D001706:Biopsy / Q000379:methods; D015153:Blotting, Western; D016022:Case-Control Studies; D002446:Celiac Disease / Q000378:metabolism / Q000503:physiopathology*; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D005903:Gliadin / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005903:Gliadin; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide