Peripheral α-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats.
| Autor: | van den Wijngaard RM; Tytgat Institute for Liver and Intestinal research, Academic Medical Center, Amsterdam, The Netherlands. r.vandenwijngaard@amc.uva.nl, Stanisor OI, van Diest SA, Welting O, Wouters MM, de Jonge WJ, Boeckxstaens GE |
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| Jazyk: | angličtina |
| Zdroj: | Neurogastroenterology and motility [Neurogastroenterol Motil] 2012 Mar; Vol. 24 (3), pp. 274-82, e111. Date of Electronic Publication: 2011 Nov 30. |
| DOI: | 10.1111/j.1365-2982.2011.01840.x |
| Abstrakt: | Background: Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of this study was to compare pre- and poststress CRF-receptor antagonist treatment protocols for their ability to, respectively, prevent and reverse mast cell dependent visceral hypersensitivity in a rat model of neonatal maternal separation. Methods: The visceromotor response to colonic distention was assessed in adult maternally separated and non-handled rats before and at different time points after 1 h of water avoidance (WA). Rats were treated with the mast cell stabilizer doxantrazole and the CRF receptor-antagonist α-helical-CRF (9-41). Western blotting was used to assess mucosal protein levels of the mast cell protease RMCP-2 and the tight junction protein occludin. Key Results: In maternally separated, but not in non-handled rats, WA induced chronic hypersensitivity (up to 30 days) to colorectal distention. Visceral hypersensitivity was prevented, but could not be reversed by administration of α-helical-CRF (9-41). In contrast, however, the mast cell stabilizer doxantrazole reversed visceral hypersensitivity. Compared with vehicle-treated rats, pre-WA α-helical-CRF (9-41) treated animals displayed higher mucosal RMCP-2 and occludin levels. Conclusions & Inferences: Water avoidance-stress leads to persistent mast cell dependent visceral hypersensitivity in maternally separated rats, which can be prevented, but not reversed by blockade of peripheral CRF-receptors. We conclude that persistent poststress mast cell activation and subsequent visceral hypersensitivity are not targeted by CRF-receptor antagonists. (© 2011 Blackwell Publishing Ltd.) |
| Databáze: | MEDLINE |
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