The response of small intestinal villous and crypt epithelium to choleratoxin in rat and guinea pig. Evidence against a specific role of the crypt cells in choleragen-induced secretion.

1. Some kinetic properties of adenylate cyclase in separately isolated upper villous and crypt cells from rat and guinea pig small intestine were compared. An apparent Km of 0.4 mM was found for both enzymes in the rat. The slight difference between the V-values measured in the fluoride-stimulated state (132 and 165 pmoles cyclic AMP formed per min per mg protein respectively) indicated an approximately equal enzyme content of both cell populations and argues strongly against a preferential localization in the brushborder region of the epithelial cell. 2. Prolonged contact of the small intestine with luminally administered choleragen led to an irreversible activation of adenylate cyclase in both villous and crypt compartments. The maximal stimulation of the upper villous enzyme (4-7 times) exceeded the maximal effect on the crypt enzyme by two-fold. 3. A lag phase of at least 30 min was found between the first luminal contact with the purified choleragen and a significant activation of the adenylate cyclase associated with isolated intestinal brushborders from the upper villous region. 4. By using a short exposure time (2 min) of the luminal surface to high amounts of choleragen, adenylate cyclase activity in the upper villus could be optimally stimulated in the absence of any alteration of crypt cell activity. 5. By comparing, in vivo, the effects of short and prolonged contact with choleratoxin on the unidirectional and net flux of ions and water in ileal and jejunal segments, it was concluded that both villous and crypt regions contribute to the secretion of water and electrolytes (sodium, chloride and bicarbonate ions) during cholera. The serosal to mucosal flux of sodium and chloride ions increased without a significant alteration of the opposite flux. These results imply that absorptive and secretory processes occur within the same epithelial compartment. 6. The view that the crypt epithelium fulfills a specific role during the choleragen-induced secretion of ions and water is incompatible with the results of the present study.