title: Peripheral α-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats.
abstract: 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.
  
  
  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
  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.
authors: Tytgat Institute for Liver and Intestinal research, Academic Medical Center, Amsterdam, The Netherlands. r.vandenwijngaard@amc.uva.nl
authors: R M
authors: RM
authors: van den Wijngaard
authors: O I
authors: OI
authors: Stanisor
authors: S A
authors: SA
authors: van Diest
authors: O
authors: O
authors: Welting
authors: M M
authors: MM
authors: Wouters
authors: W J
authors: WJ
authors: de Jonge
authors: G E
authors: GE
authors: Boeckxstaens
mesh_terms: D000818:Animals; D053818:Chymases / Q000378:metabolism; D003106:Colon / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects*; D004576:Electromyography; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006930:Hyperalgesia / Q000503:physiopathology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008426:Maternal Deprivation; D010446:Peptide Fragments / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology; D059265:Visceral Pain / Q000503:physiopathology*
chemical_list: D006727:Hormone Antagonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); C083294:chymase 2; D053818:Chymases