Abnormal anandamide metabolism in celiac disease

Battista, Natalia; Sabatino, Antonio Di; Tommaso, Morena Di; Biancheri, Paolo; Rapino, Cinzia; Vidali, Francesca; Papadia, Cinzia; Montana, Chiara; Pasini, Alessandra; Lanzini, Alberto; Villanacci, Vincenzo; Maccarrone, Mauro

doi:10.1016/j.jnutbio.2011.06.017

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…In addition, we reported that the ex vivo incubation of treated celiac biopsies with PT-gliadin significantly increased the expression of mRNA and protein of both receptors. These in vivo and ex vivo data are in agreement with previous studies, showing an alteration of the endocannabinoid system in the duodenal mucosa of UCD patients [11], [12]. Moreover, we have recently reported that mRNA, protein and activity levels of the main enzyme responsible for AEA synthesis, NAPE-PLD, are increased in UCD mucosa compared to TCD and normal mucosa [12], a finding that could provide a possible explanation for the increased AEA concentration previously shown in the mucosa of UCD patients [11].…”

Section: Discussionsupporting

confidence: 93%

“…These in vivo and ex vivo data are in agreement with previous studies, showing an alteration of the endocannabinoid system in the duodenal mucosa of UCD patients [11], [12]. Moreover, we have recently reported that mRNA, protein and activity levels of the main enzyme responsible for AEA synthesis, NAPE-PLD, are increased in UCD mucosa compared to TCD and normal mucosa [12], a finding that could provide a possible explanation for the increased AEA concentration previously shown in the mucosa of UCD patients [11]. The presence of CB 1 and CB 2 receptors has been demonstrated in different segments of the gastrointestinal tract and their involvement in disorders where intestinal inflammation and gut dysfunctions take place has been confirmed in several in vitro human studies [19], [20].…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, according to very recent papers [15], [29]–[31], it would be interesting to ascertain whether CBR gene-by-phenotype associations can be found also in this pathology, or CBR polymorphism in childhood might be considered a symptom of predisposition for celiac disease risk. In conclusion, our findings together with those published in a previous study [12], suggest that an abnormal modulation of the endocannabinoid system, both at CBR and AEA levels, may be implicated in the pathogenesis of celiac disease. Further studies are needed to ascertain whether targeting these changes might have a therapeutic role, at least in those patients who are no longer responsive to gluten-free diet.…”

Section: Discussionsupporting

confidence: 85%

“…Experimental studies demonstrated the presence of CBR in various sections of the gastrointestinal tract and a dysregulation of their expression has been reported in several gut pathologies, including diarrhoea [7], colon cancer [8], inflammatory and irritable bowel diseases [9], [10]. High AEA levels in the duodenal mucosa of untreated celiac disease (UCD) patients in comparison to treated celiac disease (TCD) patients and control subjects (CS) [11] are likely due to an altered N -acylphosphatidyl-ethanolamine specific phospholipase D (NAPE-PLD) activity [12], and might self-induce an increase of CBR, as a fine mechanism of regulation common to many diseases [11], [13], [14]. Indeed, immunofluorescence analyses showed that CB 1 protein is strongly expressed in duodenum biopsies from UCD patients [11], whereas CB 2 is up-regulated, both at transcriptional and translational levels, in small bowel biopsies obtained from children with celiac disease [15].…”

Section: Introductionmentioning

confidence: 99%

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Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

et al. 2013

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Anandamide (AEA) is the prominent member of the endocannabinoid family and its biological action is mediated through the binding to both type-1 (CB1) and type-2 (CB2) cannabinoid receptors (CBR). The presence of AEA and CBR in the gastrointestinal tract highlighted their pathophysiological role in several gut diseases, including celiac disease. Here, we aimed to investigate the expression of CBR at transcriptional and translational levels in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also biopsies from treated celiac patients cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our data show higher levels of both CB1 and CB2 receptors during active disease and normal CBR levels in treated celiac patients. In conclusion, we demonstrate an up-regulation of CB1 and CB2 mRNA and protein expression, that points to the therapeutic potential of targeting CBR in patients with celiac disease.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

et al. 2013

Self Cite

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“…Moreover, CB 1 immunoreactivity strongly increases in biopsies from patients with active celiac disease compared to healthy patients and patients after remission. Another study showed that duodenal mucosal NAPE‐PLD expression and activity are increased in untreated celiac patients compared to treated patients and healthy controls; however, in vivo mucosal FAAH expression and activity did not change in the three groups of patients …”

Section: Endocannabinoid System In Human Gi Diseasesmentioning

confidence: 97%

Toward modulation of the endocannabinoid system for treatment of gastrointestinal disease: FAAHster but not “higher”

Nasser

Bashashati

Andrews

2014

Neurogastroenterology Motil

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Cannabis has been used to treat various afflictions throughout the centuries, including nausea, vomiting, and pain. It has also been used recreationally for its psychotropic properties, which can include a pleasurable 'high' feeling and a decrease in anxiety and tension; however, other may experience dysphoria. Changes in cognition and psychomotor performance are also well-known with cannabis use. In recent years, our understanding of the endocannabinoid system (ECS) has progressed dramatically; the objective of identifying agents which may allow modulation of the ECS without significant psychotropic side effects may be possible. Inhibition of fatty acid amide hydrolase (FAAH), an important enzyme for the degradation of anandamide and other endogenous cannabinoids, is a promising target to achieve this goal. In this issue of Neurogastroenterology and Motility, Fichna and colleagues report on a novel selective FAAH inhibitor, PF-3845, with potent antinociceptive and antidiarrheal effects in a mouse model. In this context, we briefly review the components of the ECS, discuss pharmacologic targets for indirect cannabinoid receptor stimulation, and describe recent research with cannabinoids for gut disorders.

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Downstream effects of endocannabinoid on blood cells: implications for health and disease

Gasperi

Evangelista

Savini

et al. 2015

Cell. Mol. Life Sci.

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Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are the most biologically active members, are polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome proliferator-activated receptors. Depending on the target engaged, these bioactive mediators can regulate different signalling pathways, at both central and peripheral levels. The biological action of eCBs is tightly controlled by a plethora of metabolic enzymes which, together with the molecular targets of these substances, form the so-called "endocannabinoid system". The ability of eCBs to control manifold peripheral functions has received a great deal of attention, especially in the light of their widespread distribution in the body. In particular, eCBs are important regulators in blood, where they modulate haematopoiesis, platelet aggregation and apoptosis, as well as chemokine release and migration of immunocompetent cells. Here, we shall review the current knowledge on the pathophysiological roles of eCBs in blood. We shall also discuss the involvement of eCBs in those disorders affecting the haematological system, including cancer and inflammation. Knowledge gained to date underlines a fundamental role of the eCB system in blood, thus suggesting that it may represent a therapeutic promise for a broad range of diseases involving impaired hematopoietic cell functions.

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Abnormal anandamide metabolism in celiac disease

Cited by 10 publications

References 23 publications

Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

Toward modulation of the endocannabinoid system for treatment of gastrointestinal disease: FAAHster but not “higher”

Downstream effects of endocannabinoid on blood cells: implications for health and disease

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