Regulation of intestinal goblet cell secretion. II. A survey of potential secretagogues

The factors that regulate the rate of mucus secretion in intestinal goblet cells are only partially defined. Autoradiographic and ultrastructural studies demonstrated that muscarinic cholinergic agents accelerate the exocytosis of mucus from goblet cells in the crypts throughout the small and large intestine, both in vivo and in mucosal organ culture. The present study seeks to identify other factors that may alter mucous secretory rates. Mucosal explants were exposed to potential secretagogues and inhibitors in the organ-culture system and analyzed by light and electron microscopy, alpha- and beta-Adrenergic agents, gastrointestinal regulatory peptides, serotonin, histamine, and dibutyryl cyclic nucleotides were tested over wide concentration ranges. With the exception of histamine, none of these agents accelerated or inhibited the exocytosis of mucous granules. Histamine was effective at the concentration of 10(-4) M and induced rapid, compound exocytosis by crypt goblet cells in mucosal explants from the colon but not from small intestine. The response to histamine was unaffected by atropine. Goblet cells on the mucosal surface released mucus by compound exocytosis when exposed to mustard oil, a nonspecific chemical irritant, but not when exposed to histamine or cholinergic agents.