Regulation of intestinal goblet cells in situ, in mucosal explants and in the isolated epithelium.

Abstract

Cholinergic secretagogues were previously shown to accelerate mucin secretion from intestinal goblet cells of adult rats and rabbits, both in vitro and in mucosal explants. This rapid secretory response occurs only in crypt cells; surface goblet cells are not affected. Rapid secretion involves the sequential fusion of secretory granule membranes with the plasma membrane and with each other, but does not require granule movement. In unstimulated cells, slow transport of secretory granules towards the luminal cell surface depends on functional microtubules. Goblet cells appear in the rat fetal intestine three to four days before birth but they are insensitive to cholinergic agents in the fetus and neonate. The secretory response of crypt goblet cells to carbachol, both in vivo and in mucosal slices in vitro, is established throughout the intestines only after weaning (20-25 days after birth). To determine whether acetylcholine from nerve endings in the intact mucosa may mediate a mucus secretory response in the absence of exogenous secretagogues, mucosal sheets were mounted in modified Ussing chambers and goblet cell secretion was assessed after electrical field stimulation. Electrical field stimulation elicited mucus secretion from crypt (but not surface) goblet cells. Secretion was inhibited by prior treatment of the mucosa with 500 nM-tetrodotoxin or 100 microM-atropine, but not by 10 microM-atropine. Thus, endogenous nerves may regulate mucus secretion from crypt goblet cells in the intact mucosa. When intact sheets of epithelium were isolated from adult rat ileum and colon, then maintained in vitro and exposed to 20 microM-carbachol, crypt goblet cells released mucin in response to the secretagogue but goblet cells in in portions of the epithelium derived from villi or mucosal surfaces were unresponsive. This suggests that crypt epithelial cells respond directly to cholinergic agents and that they lose this sensitivity as they migrate out of the crypts.