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Unraveling ammonia transport: Role of NHE2/3 and cH/K‐ATPase
Author(s) -
Engevik Melinda Anne,
Worrell Roger T,
Shull Gary E
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.694.6
Subject(s) - chemistry , secretion , ion transporter , transporter , ammonia , butyrate , epithelial polarity , atpase , biochemistry , cell , membrane , enzyme , fermentation , gene
In liver failure, hepatic ammonia clearance is impaired; this can result in hyperammonia and hepatic encephalopathy (HE). Current therapy for HE targets colonic microflora to reduce ammonia production and thus delivered liver load. A better understanding of colonic ammonia transport mechanisms is necessary to more directly target epithelial transport. Ammonia secretion occurs in colonic epithelial cells via basolateral NH 4+ uptake mediated by NKCC1 and Rhesus glycoprotein B (RhBG). The apical ammonia exit pathway likely occurs via ion trapping involving the combined action of Rhesus glycoprotein C (RhCG) and H + transport via cH/K‐ATPase and NHE2/3. Quantitative PCR (qRT‐PCR) was used to define distal colon transporter expression in various transporter null mice to establish co‐operative function in ammonia secretion. NKCC1 and RhCG mRNA was significantly higher in distal colon of cH/KATPase −/− mice verses WT littermates. NKCC1 and RhBG mRNA were significantly decreased in distal colon of NHE3 −/− mice verses WT littermates whereas no difference was observed in NHE2 −/− mice. In addition, cH/KATPase mRNA was increased in NHE3 −/− proximal and distal colon. In the human colonic cell line T84, inhibition of NHE2/3 by amiloride resulted in decreased secretory NH 4+ flux. These data suggest that NHE3 is the principle pathway for H + exit allowing for luminal NH3 ion trapping. Supported by NIH DK079979.