Relationship of pNH3 of tubular cells to renal production of ammonia

Abstract

Renal excretion of ammonia, addition of ammonia to renal venous blood, and total renal production of ammonia were measured in acidotic dogs before and during the intravenous infusion of ammonium chloride at rates of 0.5 and 1.0 mmole/min. Infusion of ammonium chloride increased urinary excretion of ammonia, reversed the direction of diffusion of ammonia between tubular cells and blood, i.e., induced the extraction of ammonia from blood, and reduced cellular production of ammonia. Production of ammonia was an inverse function of pNH₃ of tubular cells. The infusion of ammonium lactate-N¹⁵ into one renal artery increased total ammonia excretion but decreased production of ammonia-N¹⁴ from normal blood-borne precursors. The intravenous infusion of ammonium chloride reduced extraction of glutamine from renal blood, yet increased the concentration of free glutamine in renal cortical cells. Our data suggest that an increase in pNH₃ of tubular cells results in competitive inhibition of the glutaminase-1 reaction. We further suggest that the pNH₃ of tubular cells is one factor governing renal production of ammonia; i e., the higher the cellular pNH₃, the lower is the renal production of ammonia.