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 mucu s release and mast cell degranulation and examined whether corticotrop in releasing factor (CRF) was involved in these responses. After 30-mi n immobilization, rats were killed, colonic mucosal explants were cult ured, and levels of rat mast cell protease II(RMCP II) and prostagland in E(2) (PGE(2)) were measured. Mucin release from explants was assaye d by incorporation of [H-3]glucosamine into colonic mucin and by histo logical evaluation of goblet cell depletion. Stress caused significant increases of colonic RMCP II, PGE(2), and mucin release and fecal pel let output and caused an similar to 10-fold increase in colonic mucosa l levels of cyclooxygenase-2 (COX-2) mRNA. These stress-associated cha nges were reproduced by intravenous or intracerebral injection of CRF in conscious, nonstressed rats. Pretreatment of rats with the CRF anta gonist alpha-helical-CRF(9-41), hexamethonium, atropine, or bretylium, or the mast cell stabilizer lodoxamide inhibited stress-induced relea se of RMCP II, PGE(2), 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 str ess. We conclude that CRF released during immobilization stress increa ses colonic transit via a neuronal pathway and stimulates colonic muci n secretion via activation of neurons and mast cells.