Origin of cAMP-dependent Cl- secretion from both crypts and surface epithelia of rat intestine

Abstract

Adenosine 3',5'-cyclic monophosphate (cAMP)-dependent Cl- secretion provides the ionic basis for secretory diarrhea. We quantified the spatial distribution of this process by measuring local ion conductance in crypts and surface epithelium or villi of rat late distal colon and ileum. By use of an improved voltage-scanning technique, the tissue was clamped to a 30-Hz sine-wave current and the electrical field above the respective structures was sensed by a stepping glass microelectrode. Under control conditions, crypts and surface epithelium contributed 61 and 39%, respectively, to the total ion conductance of distal colon. Theophylline (10 mM) increased crypt conductance (Gc) by 64% from 2.5 +/- 0.2 to 4.1 +/- 0.3 mS/cm2 and surface epithelium conductance (Gs) by 69% from 1.6 +/- 0.1 to 2.7 +/- 0.1 mS/cm2. These changes in local conductances were completely Cl- dependent, since theophylline had no effect when Cl- was replaced by gluconate. Similar results were obtained when Cl- secretion was elicited by prostaglandin E1 (1 microM) or by dibutyryl-cAMP (DBcAMP, 1 mM). After stimulation, the Cl- channel blocker 5-nitro-2-(3-phenyl-propylamino)benzoic acid (1 mM) decreased both Gc and Gs. In rat ileum, theophylline plus DBcAMP caused an increase in total conductance of 19% only because of its large paracellular conductance. The ratio of scanning signals above villi and intervillous spaces was unaffected, indicating that Cl- conductance is induced in both crypts and villi. We conclude that in distal large intestine cAMP-dependent Cl- secretion is not confined to crypts but is evenly performed also by surface cells. A similar distribution exists in small intestine.