AJP - Cell Physiology, Vol 273, Issue 2 C634-C642, Copyright © 1997 by American Physiological Society

ARTICLES

Ammonia effect on calcium-activated chloride secretion in T84 intestinal epithelial monolayers

J. M. Mayol, B. J. Hrnjez, H. I. Akbarali, J. C. Song, J. A. Smith and J. B. Matthews
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA.

We recently showed that ammonia profoundly inhibits cyclic nucleotide-regulated Cl- secretion in model human T84 intestinal epithelia but does not impair the secretory response to the Ca2+ agonist carbachol. Using transepithelial transport, fura 2 fluorescence, and radioisotopic efflux techniques, we further explored this dichotomy and arrived at a preliminary explanation for the inhibitory action of ammonia. The secretory response to the Ca(2+)-adenosinetriphosphatase inhibitor thapsigargin is unaffected by ammonia, which suggests that an increase in intracellular Ca2+ stimulates secretory pathways that are insensitive to ammonia. Surprisingly, Cl- secretion elicited by the Ca2+ ionophores ionomycin and A23187 is markedly blunted in monolayers pretreated with ammonia. However, ammonia posttreatment does not inhibit the secretory response to ionophore, which suggests that ammonia may interfere with the ability of these ionophores to increase intracellular [Ca2+]. This hypothesis is directly supported by fura 2 experiments. The inhibitory action of ammonia parallels the behavior of the K+ channel blocker Ba2+, and ammonia reduces the basolateral 86Rb+ efflux rate constant in forskolin- but not in carbachol-treated monolayers. Ammonia, which is present in high concentrations in the normal gastro-intestinal tract, may serve as a novel endogenous regulator of epithelial electrolyte transport by interfering with a Ba(2+)-sensitive basolateral K+ conductance distinct from the Ca(2+)-activated basolateral K+ conductance.

This article has been cited by other articles:

				R. T. Worrell, A. Best, O. R. Crawford, J. Xu, M. Soleimani, and J. B. Matthews Apical ammonium inhibition of cAMP-stimulated secretion in T84 cells is bicarbonate dependent Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G768 - G778. [Abstract] [Full Text] [PDF]

				R. T. Worrell, J. Oghene, and J. B. Matthews Ammonium effects on colonic Cl- secretion: anomalous mole fraction behavior Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G14 - G22. [Abstract] [Full Text] [PDF]

				S. J. Hagen, H. Wu, and S. W. Morrison NH4Cl inhibition of acid secretion: possible involvement of an apical K+ channel in bullfrog oxyntic cells Am J Physiol Gastrointest Liver Physiol, August 1, 2000; 279(2): G400 - G410. [Abstract] [Full Text] [PDF]

				B. J. Hrnjez, J. C. Song, M. Prasad, J. M. Mayol, and J. B. Matthews Ammonia blockade of intestinal epithelial K+ conductance Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G521 - G532. [Abstract] [Full Text] [PDF]