Acute stress causes mucin release from rat colon: role of
corticotropin releasing factor and mast cells.
Castagliuolo, Ignazio, J. Thomas Lamont, Bosheng Qiu, Sheila M.
Fleming, K. Ramakrishnan Bhaskar, Sigfus T. Nikulasson, Conan
Kornetsky, and Charalabos Pothoulakis.
Division of Gastroenterology, Beth Israel Hospital, Harvard Medical
School, Boston, MA 02215 and Sections of Gastroenterology and
Departments of Pharmacology and Pathology, Evans Memorial Department
of Clinical Research, Boston University School of Medicine, Boston,
MA 02118
APStracts 3:0126G, 1996.
We determined the effects of immobilization stress on rat colonic
mucus release and mast cell degranulation and examined whether
corticotropin releasing factor (CRF) was involved in these responses.
After 30 min immobilization, rats were killed, colonic mucosal
explants were cultured and levels of rat mast cell protease II
(RMCPII), and prostaglandin E2 (PGE2) were measured. Mucin release
from explants was assayed by incorporation of [3H]-glucosamine into
colonic mucin and by histological evaluation of goblet cell
depletion. Stress caused significant increases of colonic RMCPII,
PGE2, and mucin release and fecal pellet output and caused an 10-fold
increase in colonic mucosal levels of cyclooxygenase-2 (COX-2) mRNA.
These stress-associated changes were reproduced by intravenous or
intracerebral injection of CRF in conscious, non-stressed rats.
Pretreatment of rats with the CRF antagonist (-helical-CRF9-41,
hexamethonium, atropine, or bretylium or the mast cell stabilizer
lodoxamide inhibited stress-induced release of RMCPII, PGE2, and
mucin, while indomethacin prevented mucin release but not mast cell
degranulation. Hexamethonium and CP-96,345, a substance P antagonist,
inhibited fecal pellet output caused by stress. We conclude that CRF
released during immobilization stress increases colonic transit via a
neuronal pathway, and stimulates colonic mucin secretion via
activation of neurons and mast cells.
Received 17 November 1995; accepted in final form 6 June 1996.
APS Manuscript Number G493-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96