Secretagogue response of goblet cells and columnar cells in human colonic crypts

Crypts of Lieberkühn were isolated fromhuman colon, and differential interference contrast microscopydistinguished goblet and columnar cells. Activation with carbachol(CCh, 100 µM) or histamine (10 µM) released contents from gobletgranules. Stimulation with prostaglandinE₂(PGE₂, 5 µM) or adenosine (10 µM) did not release goblet granules but caused the apical margin ofcolumnar cells to recede. Goblet volume was lost during stimulationwith CCh or histamine (~160 fl/cell), but not withPGE₂ or adenosine. Three-quartersof goblet cells were responsive to CCh but released only 30% of gobletvolume. Half-time for goblet volume release was 3.7 min.PGE₂ stimulated a prolonged fluidsecretion that attained a rate of ~350 pl/min. Columnar cells lost~50% of apical volume during maximalPGE₂ stimulation, with a half-timeof 3.3 min. In crypts from individuals with ulcerative colitis, goblet cells were hypersensitive to CCh for release of goblet volume. Theseresults support separate regulation for mucus secretions from gobletcells and from columnar cells, with control mechanisms restrictingtotal release of mucus stores.