Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.
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PMID:Endocannabinoids modulate apoptosis in endometriosis and adenomyosis. 2854 92

The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.
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PMID:Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis. 3083 39