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

Abstract

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.

Luminal leptin activates mucin-secreting goblet cells in the large bowel

“…Goblet cells secrete mucin via an unregulated constitutive pathway that is dependent on the continuous movement of mucin granules from the Golgi apparatus to the apex of the cell and by a regulated process dependent on the sudden release of mucin from granules. This regulatory process is controlled by a wide variety of stimuli, including nerve activation and inflammatory mediators (6,31,33). In this study, we clearly demonstrated that leptin is one of these stimuli.…”

Proteinases of Pseudomonas aeruginosa evoke mucin release by tracheal epithelium.

“…Originally, it was thought that goblet cells extrude a single mass of mucus through a break in the apical plasma membrane (40-45). Subsequent studies of intestinal goblet cells by Specian and Neutra (46) have demonstrated compound exocytosis which can be evoked by a variety of secretagogues (47). A similar sequence has been observed in goblet cells of the cat trachea (Tandler, B., unpublished observations).…”

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

“…Although great advances have been made in recent years in identifying distinct mucin genes and types of mucins, most studies of mucus release have focused on histological changes associated with mucus-secreting cells and the thickness of the extrinsic mucus layers on epithelia (26,(30)(31)(32).…”