Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats.
OBJECTIVE
Intestinal mast cell activity is modulated by the central nervous system, but the mechanisms are not well established. The aim of this study was to investigate whether cerebral thyrotropin-releasing 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 anesthetized rats, mast cell activation was assessed by measuring the release of the specific mucosal rat mast cell protease II (RMCP II) and prostaglandin (PG) D2 into the intestinal lumen. Luminal protein release was measured as an index of epithelial permeability to macromolecules.


RESULTS
Intracisternal injection of the TRH analogue RX 77368 (30 ng) induced a transient increase in intestinal release of RMCP II and PGD2 that was abolished by dox-antrazole. RX 77368-stimulated RMCP II release was also abolished by vagotomy and reduced by atropine by 65%. However, both systemic capsaicin and indo-methacin enhanced RMCP II release. RX 77368-stimulated luminal protein release was abolished by vagotomy and reduced by doxantrazole.


CONCLUSIONS
Central vagal activation by TRH stimulates intestinal mast cell secretion, in part via peripheral muscarinic receptors, and is modulated by PGs and capsaicin-sensitive afferent innervation. Intestinal mast cell activation contributes to the TRH analogue-stimulated luminal protein release.
Santos
J
J
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Saperas
E
E
Mourelle
M
M
Antolín
M
M
Malagelada
J R
JR
D000818:Animals; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease; D015230:Prostaglandin D2; D011761:Pyrrolidonecarboxylic Acid