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Neuroimmune Mechanisms of Intestinal Responses to Stress: Role of Corticotropin-Releasing Factor and Neurotensin

Authors

  • CHARALABOS POTHOULAKIS,

    Corresponding author
    1. Division of Gastroenterology, Beth Israel Deaconess, Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA
      Address for correspondence: Charalabos Pothoulakis, M.D., Division of Gastroenterology, Dana 601, Beth Israel Deaconess Hospital, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; Telephone: 617-667-1259; Fax: 617-975-5071.
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  • IGNAZIO CASTAGLIUOLO,

    1. Division of Gastroenterology, Beth Israel Deaconess, Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA
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  • SUSAN E. LEEMAN

    1. Department of Pharmacology, Boston University Medical Center Hospital, Boston University School of Medicine, Boston, Massachusetts 02118 USA
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Address for correspondence: Charalabos Pothoulakis, M.D., Division of Gastroenterology, Dana 601, Beth Israel Deaconess Hospital, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215; Telephone: 617-667-1259; Fax: 617-975-5071.

Abstract

Abstract: 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 α-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.

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