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Brain Res Bull. 2018 May;139:224-234. doi: 10.1016/j.brainresbull.2018.02.012. Epub 2018 Feb 10.

Modulation of central endocannabinoid system results in gastric mucosal protection in the rat.

Author information

1
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
2
Department of Pharmacology and Pharmacotherapy, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
3
MTA-SE NAP B Cognitive Translational Behavioural Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
4
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary. Electronic address: gyires.klara@med.semmelweis-univ.hu.

Abstract

Previous findings showed that inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), degrading enzymes of anandamide (2-AEA) and 2-arachidonoylglycerol (2-AG), reduced the nonsteroidal anti-inflammatory drug-induced gastric lesions. The present study aimed to investigate: i./whether central or peripheral mechanism play a major role in the gastroprotective effect of inhibitors of FAAH, MAGL and AEA uptake, ii./which peripheral mechanism(s) may play a role in mucosal protective effect of FAAH, MAGL and uptake inhibitors.

METHODS:

Gastric mucosal damage was induced by acidified ethanol. Gastric motility was measured in anesthetized rats. Catalepsy and the body temperature were also evaluated. Mucosal calcitonin gene-related peptide (CGRP), somatostatin concentrations and superoxide dismutase (SOD) activity were measured. The compounds were injected intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.).

RESULTS:

1. URB 597, JZL184 (inhibitors of FAAH and MAGL) and AM 404 (inhibitor of AEA uptake) decreased the mucosal lesions significantly given either i.c.v. or i.p. 2. URB 937, the peripherally restricted FAAH inhibitor failed to exert significant action injected i.p. 3. Ethanol-induced decreased levels of mucosal CGRP and somatostatin were reversed by URB 597, JZL 184 and AM 404, the decreased SOD activity was elevated significantly by URB 597 and JZL 184. 4. Neither compounds given i.c.v. influenced gastric motility, elicited catalepsy, or hypothermia.

CONCLUSION:

Elevation of central endocannabinoid levels by blocking their degradation or uptake via stimulation of mucosal defensive mechanisms resulted in gastroprotective action against ethanol-induced mucosal injury. These findings might suggest that central endocannabinoid system may play a role in gastric mucosal defense and maintenance of mucosal integrity.

KEYWORDS:

Anandamide uptake blockade; Endocannabinoids; FAAH; Gastric lesion; MAGL; Rat

[Indexed for MEDLINE]

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