Abstract
AFTER exposure to secretagogues the small intestine changes from a tissue that absorbs fluid and electrolyte from lumen to blood into a tissue that secretes electrolyte and fluid into the lumen1–4. It has been shown that this secretion results from an increase in the passive Cl− permeability of the mucosal border, which permits Nad to leak passively from the lateral intercellular spaces, where it is present at hypertonic concentrations5, into the mucosal bathing solution. Na+ and water, electroosmotically coupled to Na+ movement, leak through the tight junctions1,2, and Cl− leaks through relatively anhydrous anion-selective channels, induced withira the mucosal border by secretagogues. The increased reflux of NaCl from the lateral intercellular space accounts for both the apparent decrease in electroneutral NaCl uptake across the mucosal border induced by secretagogues and the apparent increase in active CP secretion and short-circuit current3,6,7. We have investigated the mechanism by which intestinal secretagogues increase passive Cl− permeability and thereby cause secretion. Cl− permeability is increased by several secretagogues, some of which, such as theophylline and choleragen, increase intracellular cyclic AMP concentration, and others, such as A23187, the Ca2+ ionophore, or carbachol, do not8. Thus there has been no known common mode of secretory induction. To investigate this problem we used two drugs that prevent intestinal secretion in vitro, RMI 12330A (Richardson Merrell), and the antipsychotic pheno-thiazine trifluoperazine (Stelazine, Smith, Kline and French). RMI 12330A prevents secretion by inhibiting choleragen-induced adenylyl cyclase activity9. Stelazine inhibits phosphodiesterase in tissues11,12 by preventing the activation of the enzyme by Ca2+-dependent regulator protein, CDR. We report here that it also inhibits Cl− secretion and binds to CDR.
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ILUNDAIN, A., NAFTALIN, R. Role of Ca2+-dependent regulator protein in intestinal secretion. Nature 279, 446–448 (1979). https://doi.org/10.1038/279446a0
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DOI: https://doi.org/10.1038/279446a0
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