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MUCOSAL BIOLOGY

Ammonium effects on colonic Cl^- secretion: anomalous mole fraction behavior

¹Epithelial Pathobiology Group, Department of Surgery and ²Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45219

Submitted 29 April 2003 ; accepted in final form 20 August 2003

A significant amount of ammonium () is absorbed by the colon. The nature of effects on transport and transport itself in colonic epithelium is poorly understood. The goal of this study was to elucidate the effects of on cAMP-stimulated Cl^- secretion in the colonic cell line T84. In HEPES-buffered solutions, application of basolateral resulted in a reduced level of Cl^- secretory current. The effect of appears to occur by at least three mechanisms: 1) basolateral membrane depolarization, 2) a competitive effect with K⁺, and 3) a long-term (>20 min) increase in transepithelial resistance (TER). The competitive effect with K⁺ exhibits anomalous mole fraction behavior. Transepithelial current relative to that in 10 mM basolateral K⁺ was inhibited 15% by 10 mM alone and by 30% with a mixture of 2 mM K⁺ and 8 mM . A mole fraction mix of 2 mM K⁺:8 mM produced a greater inhibition of basolateral membrane K⁺ current than pure K⁺ or alone. Similar anomalous behavior was also observed for inhibition of bumetanide-sensitive ³⁶Cl^- uptake, e.g., Na⁺-K⁺-2Cl^--cotransporter (NKCC-1). No anomalous effect was observed on Na⁺-K⁺-ATPase current. Both NKCC-1 and Na⁺-K⁺-ATPase activity were elevated in 10 mM with respect to 10 mM K⁺. The effect on TER did not exhibit anomalous mole fraction behavior. The overall effect of basolateral on cAMP-stimulated transport is dependent on the ratio at the basolateral membrane, where o is outside of the cell.

transepithelial resistance; Na⁺-K⁺-2Cl^--cotransporter

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