Mechanism of intestinal secretion. Effect of serotonin on rabbit ileal crypt and villus cells.

To determine the mechanism of action of an intestinal secretagogue, serotonin, we have isolated crypt and villus cells and demonstrated Na:H and Cl:HCO3 exchange activity using the intracellular pH-sensitive fluorescent dye, 2,7-bis (carboxy-ethyl)-5,6-carboxy-fluorescein. Serotonin alkalinized both crypt and villus cells. Alkalinization in villus cells was HCO3 dependent and Na independent. In contrast, alkalinization in crypt cells was HCO3 independent and Na dependent. In villus cells, recovery from an alkaline load induced by Cl removal, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or propionate pulse, known to occur via the Cl:HCO3 exchange, is inhibited by serotonin. In contrast, in crypt cells, recovery from an acid load induced by Na removal, amiloride and NH4Cl pulse, known to occur via Na:H exchange, is stimulated by serotonin. These data suggest that serotonin is inhibiting Cl:HCO3 exchange in villus cells and stimulating Na:H exchange in crypt cells. These effects of serotonin would be expected to inhibit coupled Na and Cl absorption by villus cells and stimulate HCO3 secretion by crypt cells in the intact ileum.