Hormonal and Na+ effect on renal glutamine uptake

Area of Science:

• Renal Physiology
• Biochemistry

Background:

• Cellular and extracellular pathways exist for glutamine metabolism in the kidney.
• The relative contribution of these pathways to renal ammoniagenesis is not fully understood.

Purpose of the Study:

• To investigate the competition between membrane glutamine transporters and extracellular hydrolysis.
• To determine how acid-base balance and glucocorticoids modulate glutamine flux through cellular and extracellular pathways.

Main Methods:

• Isolated perfused rat kidneys (nonacidotic and chronically acidotic) were used.
• Glutamine flux was measured using sodium-containing and sodium-free (choline-substituted) media.
• The role of adrenals and glucocorticoids was studied in adrenalectomized rats supplemented with triamcinolone.

Main Results:

• Sodium gradient elimination abolished glutamine reabsorption but not utilization, leading to extracellular glutamate accumulation.
• Acidotic kidneys showed increased glutamine utilization and ammonia production compared to nonacidotic kidneys.
• Adrenalectomy reduced glutamine transport, utilization, and ammonia production, increasing extracellular glutamate, while triamcinolone restored cellular pathway flux.

Conclusions:

• Two renal glutaminases operate in situ, with their contributions modulated by acid-base balance and glucocorticoids.
• The sodium gradient influences glutamine flux, favoring cellular transport under normal conditions.
• Extracellular hydrolysis becomes more prominent in acidosis and adrenal insufficiency, impacting renal ammoniagenesis.