Acute stress causes mucin release from rat colon: role of corticotropin releasing factor and mast cells.
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 (RMCP II) 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 RMCP II, PGE2, and mucin release and fecal pellet output and caused an approximately 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, nonstressed rats. Pretreatment of rats with the CRF antagonist alpha-helical-CRF9-41, hexamethonium, atropine, or bretylium, or the mast cell stabilizer lodoxamide inhibited stress-induced release of RMCP II, PGE2, and mucin, whereas 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.
Castagliuolo
I
I
Division of Gastroenterology, Beth Israel Hospital, Harvard Medical School, Boston 02215, USA.
Lamont
J T
JT
Qiu
B
B
Fleming
S M
SM
Bhaskar
K R
KR
Nikulasson
S T
ST
Kornetsky
C
C
Pothoulakis
C
C
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001949:Bretylium Compounds / Q000494:pharmacology; D003106:Colon; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D009077:Mucins / Q000096:biosynthesis / Q000378:metabolism*; D009924:Organ Culture Techniques; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012697:Serine Endopeptidases / Q000378:metabolism*; D013315:Stress, Psychological / Q000503:physiopathology*; D014158:Transcription, Genetic
D001713:Biphenyl Compounds; D001949:Bretylium Compounds; D006727:Hormone Antagonists; D007527:Isoenzymes; D008565:Membrane Proteins; D009077:Mucins; D010446:Peptide Fragments; D012333:RNA, Messenger; D018738:Hexamethonium; D001285:Atropine; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease; D015232:Dinoprostone; D005944:Glucosamine; D010072:Oxamic Acid; C045166:bretylium; C021702:lodoxamide ethyl; C066892:CP 96345; D007213:Indomethacin