Effects of 2,4-dinitrophenol on renal ammoniagenesis in the rat

Injection of anesthetized rats with the uncoupling agent, 2,4-dinitrophenol (2,4-DNP) 10 or 20 mg/kg induced a systemic hyperammonemia unaccompanied by blood acid-base status changes and related to an increased release of ammonium from the kidney into the renal vein. Ammonium excretion into the urine did not increase. The renal uptake of circulating glutamine rose. The antiepileptic drug sodium valproate (VPA), a short-chain, branched fatty acid, had the same effects on rat and man. These findings suggest that VPA stimulates renal ammoniagenesis by the same mechanisms as 2,4-DNP.