Neuroimmune mechanisms of intestinal responses to stress. Role of corticotropin-releasing factor and neurotensin.
Previous studies showed that exposure of experimental animals to immobilization stress increases colonic motility and that these effects are mediated by release of corticotropin-releasing factor (CRF), Studies from our laboratory showed that 30-min immobilization stress of rats caused several not previously described colonic responses to stress, including increased colonic mucin and prostaglandin E2 (PGE2) secretion, increased colonic mucosal levels of cyclooxygenase-2 (COX-2) mRNA, and degranulation of colonic mast cells. These stress-associated colonic changes were reproduced by intravenous or intracerebral injection of CRF in conscious, nonstressed rats. Furthermore, pretreatment of rats with the CRF antagonist alpha-helical CRF9-41, hexamethonium, or the mast cell stabilizer lodoxamide inhibited our observed colon responses to immobilization stress. Our results indicate that CRF released during immobilization stress increases colonic transit via a neuronal pathway and stimulates colonic mucin release via activation of neurons and colonic mast cells. These results provide support for an important role for CRF in stress-mediated colonic responses and a link between the nervous and the immune systems.
Pothoulakis
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Division of Gastroenterology, Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Castagliuolo
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Leeman
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D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007422:Intestines / Q000503:physiopathology*; D009420:Nervous System / Q000503:physiopathology*; D009496:Neurotensin / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*
D009496:Neurotensin; D003346:Corticotropin-Releasing Hormone