Intra- and inter-nephron heterogeneity of ammoniagenesis in rats: effects of chronic metabolic acidosis and potassium depletion

Abstract

In order to determine intra- and inter-nephron heterogeneity of ammoniagenesis, ammoniagenic activity in microdissected nephron segments of control, acidotic and potassium (K)-depleted rats was examined. Intranephron distribution of ammoniagenic activity in control rats revealed the highest amount at the second segment of the proximal tubule (S2). Chronic metabolic acidosis induced ammoniagenesis markedly at the first segment of the proximal tubule (S1) by 235% and the thick ascending limb of Henle's loop by 198% and moderately at the S2 by 49%. K-depletion increased ammonia production significantly in the S1 by 298% and the S2 by 107%, which is a pattern quite similar to the result of chronic metabolic acidosis. Ammonia production in K-depletion was also increased in the cortical and medullary collecting tubule by 71% and 102%, respectively, probably due to increases in protein amounts (41% and 158%, respectively) there. To evaluate inter-nephron heterogeneity of ammoniagenesis, ammonia formation from glutamine in the S1 of superficial (SF) and juxtamedullary (JM) nephrons was examined. Although there was no difference in ammonia production between SF-S1 and JM-S1 in control rats, ammonia production in SF-S1 was significantly higher than that in JM-S1 in both metabolic acidosis and K-depletion. From these studies, we conclude: The increase of ammonia production in the proximal tubule was quite similar in both acidosis and K-depletion, suggesting that the main trigger of ammoniagenesis in both conditions might be a reduction of intracellular pH. SF-S1 was the nephron most reactive to acidosis and K-depletion. JM nephrons could be considered to be important not for ammonia production but for ammonia secretion.