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H+/solute-induced intracellular acidification leads to selective activation of apical Na+/H+ exchange in human intestinal epithelial cells

Lookup NU author(s): Professor David Thwaites, Professor Dianne Ford, Dr Michael Glanville, Professor Nicholas Simmons


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The intestinal absorption of many nutrients and drug molecules is mediated by ion-driven transport mechanisms in the intestinal enterocyte plasma membrane. Clearly, the establishment and maintenance of the driving forces - transepithelial ion gradients - are vital for maximum nutrient absorption. The purpose of this study was to determine the nature of intracellular pH (pH(i)) regulation in response to H+-coupled transport at the apical membrane of human intestinal epithelial Caco-2 cells. Using isoform-specific primers, mRNA transcripts of the Na+/H+ exchangers NHE1, NHE2, and NHE3 were detected by RT-PCR, and identities were confirmed by sequencing. The functional profile of Na+/H+ exchange was determined by a combination of pH(i), 22Na+ influx, and EIPA inhibition experiments. Functional NHE1 and NHE3 activities were identified at the basolateral and apical membranes, respectively. H+/solute-induced acidification (using glycylsarcosine or β-alanine) led to Na+-dependent, EIPA-inhibitable pH(i) recovery or EIPA-inhibitable 22Na+ influx at the apical membrane only. Selective activation of apical (but not basolateral) Na+/H+ exchange by H+/solute cotransport demonstrates that coordinated activity of H+/solute symport with apical Na+/H+ exchange optimizes the efficient absorption of nutrients and Na+, while maintaining phi and the ion gradients involved in driving transport.

Publication metadata

Author(s): Thwaites DT, Ford D, Glanville M, Simmons NL

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Investigation

Year: 1999

Volume: 104

Issue: 5

Pages: 629-635

Print publication date: 01/09/1999

ISSN (print): 0021-9738

ISSN (electronic): 1558-8238

Publisher: American Society for Clinical Investigation


DOI: 10.1172/JCI7192

PubMed id: 10487777


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