REGULATION OF INTESTINAL MAST-CELLS AND LUMINAL PROTEIN RELEASE BY CEREBRAL THYROTROPIN-RELEASING-HORMONE IN RATS

Background & Aims: Intestinal mast cell activity is modulated by the c entral nervous system, but the mechanisms are not well established. Th e aim of this study was to investigate whether cerebral thyrotropin-re leasing hormone (TRH) activates intestinal mast cells and to elucidate the mechanisms involved, specifically, the contribution of mast cells to vagally stimulated luminal protein release. Methods: In anesthetiz ed rats, mast cell activation was assessed by measuring the release of the specific mucosal rat mast cell protease II (RMCP II) and prostagl andin (PG) D-2 into the intestinal lumen. Luminal protein release was measured as an index of epithelial permeability to macromolecules. Res ults: Intracisternal injection of the TRH analogue RX 77368 (30 ng) in duced a transient increase in intestinal release of RMCP II and PGD(2) that was abolished by doxantrazole. RX 77368-stimulated RMCP II relea se was also abolished by vagotomy and reduced by atropine by 65%. Howe ver, both systemic capsaicin and indomethacin enhanced RMCP II release . RX 77368-stimulated luminal protein release was abolished by vagotom y and reduced by doxantrazole. Conclusions: Central vagal activation b y TRH stimulates intestinal mast cell secretion, in part via periphera l muscarinic receptors, and is modulated by PGs and capsaicin-sensitiv e afferent innervation. Intestinal mast cell activation contributes to the TRH analogue-stimulated luminal protein release.