Ammonia transport mediated by urea transporter A isoforms
N Pina-Lopes1, J Kabutomori1, R Campos1
1Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil.
Biology Open
|June 6, 2025
Summary
Urea transporters (UTs) facilitate urea, water, and ammonia transport in the kidney. This study reveals UT-A2 and UT-A3 enhance membrane ammonia permeability, impacting kidney function and acid-base balance.
Area of Science:
- Renal physiology
- Membrane transport
- Molecular biology
Background:
- Urea transporters (UTs) are crucial for kidney urine concentration.
- UT-A2, UT-A3, and UT-B are known to transport urea and water.
- UT-B also transports ammonia (NH3), but UT-A-mediated NH3 transport remains uncharacterized.
Purpose of the Study:
- To characterize the urea, water, and NH3 transport properties of murine UT-A2, UT-A3, and UT-B.
- To investigate the physiological relevance of UT-A-mediated NH3 transport in renal function and acid-base homeostasis.
Main Methods:
- Heterologous expression of murine UT-A2, UT-A3, and UT-B in *Lithobates catesbeianus* oocytes.
- Assessment of surface protein expression via lysine-biotinylation and immunoblotting.
- Measurement of urea uptake (radiolabeled urea), water permeability (video microscopy), and NH3 transport (surface pH microelectrode).
Main Results:
- All expressed UTs were correctly translated, glycosylated, and inserted into the oocyte membrane.
- UT-expressing oocytes showed significantly increased urea, water, and NH3 transport compared to controls.
- Phloretin treatment and specific pore mutations (Thr to Val) attenuated UT-mediated transport of all three solutes.
Conclusions:
- UT-A2 and UT-A3, for the first time, are shown to increase membrane NH3 permeability.
- UTs play a role beyond urinary concentration, potentially influencing acid-base homeostasis.
- These findings suggest UTs contribute to various physiological and pathophysiological processes.
Keywords:
Lithobates oocytesAmmonia transportMembrane permeabilityProtein structure/functionRenal functionRenal physiologySite-directed mutagenesisSurface expressionSurface pHUrea transporterUrinary concentrationWater transportMore Related Videos
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