scholarly journals Effect of monoacylglycerol lipase inhibition on intestinal permeability in chronic stress model

2020 ◽  
Vol 525 (4) ◽  
pp. 962-967
Author(s):  
Jing Wang ◽  
Xiaohua Zhang ◽  
Chongmei Yang ◽  
Shulei Zhao
2020 ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Zhang ◽  
Chongmei Yang ◽  
Shulei Zhao

Abstract Background: The endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid, which is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). The present study aimed to explore the effects of inhibition of MAGL on intestinal permeability. Methods: We first tested it in differentiated CaCO2 cells after 21 days’ culture. The rat model of water avoidance stress (WAS) was established, and rats were divided into four groups according to intervention. Rats received intraperitoneal injection (i.p.) of an MAGL inhibitor (JZL184) alone, JZL184 and the cannabinoid receptor 1 (CB1) antagonist (SR141716A), JZL184 and a cannabinoid receptor 2 (CB2) antagonist (AM630) or vehicle alone (control). We analyzed the fluorescein isothiocyanate-dextran (FD4) permeability and 2-AG level. Expression of MAGL and tight-junction-associated proteins were detected by western blot. Results: Compared with the control group, MAGL expression was higher and 2-AG levels lower among WAS rats. Intestinal permeability was increased following administration of JZL184 which occurred due to up-regulation of tight-junction-associated proteins Claudin-1, Claudin-2, Claudin-5 and Occludin.Conclusion: The effects of MAGL inhibition were mediated by CB1, indicating that MAGL may represent a novel target for the treatment of reduced intestinal permeability in the context of chronic stress.


2014 ◽  
Vol 39 (7) ◽  
pp. 1763-1776 ◽  
Author(s):  
Peng Zhong ◽  
Wei Wang ◽  
Bin Pan ◽  
Xiaojie Liu ◽  
Zhen Zhang ◽  
...  

SURG Journal ◽  
2014 ◽  
Vol 7 (3) ◽  
pp. 21-29
Author(s):  
Rachel I. Downey ◽  
Cheryl L. Limebeer ◽  
Heather I. Morris ◽  
Linda A. Parker

This study investigates the role of the endocannabinoid 2-arachidonyl glycerol (2-AG) in regulating acute and anticipatory nausea in rats using the conditioned gaping model. The animals were systemically pretreated with MJN110, a selective monoacylglycerol lipase (MAGL) inhibitor, to enhance endogenous levels of 2-AG. Acute nausea was assessed using the taste reactivity model in which a flavour, saccharin, was paired with the administration of the emetic agent, lithium chloride (LiCl). Anticipatory nausea was assessed using a model of contextually elicited conditioned gaping in which a context was paired with the emetic agent, LiCl. Results indicated that MJN110 at the 10.0 mg kg-1 and 20.0 mg kg-1 dosage significantly attenuated acute and anticipatory nausea, as displayed by the significant reduction in mean number of gapes. This suppression was mediated by CB1 receptor activation as displayed by reversal of such effects when MJN110 was coadministered with the CB1 receptor antagonist, SR 141716. The results suggest that enhancement of endogenous 2-AG levels by MAGL inhibition may have anti-emetic potential. Keywords: 2-arachidonyl glycerol; monoacylglycerol lipase; endocannabinoid; nausea; conditioned gaping; CB1 receptor


2013 ◽  
Vol 47 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Yingcong Yu ◽  
Rui Wang ◽  
Chunbai Chen ◽  
Xia Du ◽  
Lina Ruan ◽  
...  
Keyword(s):  

2006 ◽  
Vol 211 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Gary B. Quistad ◽  
Rebecka Klintenberg ◽  
Pierluigi Caboni ◽  
Shannon N. Liang ◽  
John E. Casida

2017 ◽  
Vol 651 ◽  
pp. 16-20 ◽  
Author(s):  
Yan-Na Lian ◽  
Jin-Long Chang ◽  
Qi Lu ◽  
Yi Wang ◽  
Ying Zhang ◽  
...  

Reproduction ◽  
2003 ◽  
pp. 801-808 ◽  
Author(s):  
ML Mariani ◽  
DR Ciocca ◽  
AS Gonzalez Jatuff ◽  
M Souto

A chronic unpredictable stress model used to produce depressive disorders in adult rats was applied to neonatal rats to investigate whether this type of stress can induce changes in the expression of Hsp70 and oestrogen receptor alpha in the oviduct, as detected by immunohistochemistry. Rats stressed during neonatal development showed changes in the expression pattern of Hsp70. In neonatal control rats, Hsp70-positive cells observed in the isthmus did not show any changes. Moreover, rats exposed to this stress model that reached adulthood had higher expression of Hsp70 in the isthmus (P<0.01) but not in the ampulla during oestrus than did the control rats. In contrast, during dioestrus, no significant changes were noted in adult rats that were stressed during neonatal development or in rats that were stressed in adulthood. These findings indicate that the isthmus is very sensitive to stressful stimuli and that repeated pre-weaning stress can change the expression of heat shock proteins in early and adult life. These subtle changes of expression in the oviduct did not affect the fertility of the rats that reached adulthood or that were mated under unstressed conditions. However, the control animals stressed during adulthood showed a disruption of the oestrous cycle: this finding is not observed in rats stressed during neonatal development that show an attenuated oestrous cycle disruption induced by chronic stress in adulthood. Moreover, there was dissociation between the expression of oestrogen receptor alpha and Hsp70. The amount of oestrogen receptor alpha remained constant in the epithelium of the oviduct in the control and in the stressed rats. Expression of oestrogen receptor alpha was noted in the stroma of the oviduct without the concomitant expression of Hsp70. It is possible that in certain cells and tissues Hsp70 is not necessary for oestrogen receptor alpha to be functional or Hsp70 might be present at very low amounts but is sufficient for the receptor to function.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sonali N. Reisinger ◽  
Thomas Wanek ◽  
Oliver Langer ◽  
Daniela D. Pollak

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