Effect of bath and luminal potassium concentration on ammonia production and secretion by mouse proximal tubules perfused in vitro.

Abstract

To determine the effects of acute changes in K+ concentration in vitro on ammonia production and secretion by the proximal tubule, we studied mouse S2 segments perfused with and bathed in Krebs-Ringer bicarbonate buffers containing various K+ concentrations. All bath solutions contained L-lutamine as the ammoniagenic substrate. High bath and luminal K+ concentrations (8 mM), but not high luminal K+ concentration alone, inhibited total ammonia production rates by 26%, while low bath and luminal K+ concentrations (2 mM), but not low luminal K+ concentration alone, stimulated total ammonia production rates by 33%. The stimulation of ammonia production by low bath K+ concentration was not observed when L-glutamine was added to the luminal perfusion solution. On the other hand, high luminal K+ concentration stimulated, while low luminal K+ concentration inhibited, net luminal secretion of total ammonia in a way that was: (a) independent of total ammonia production rates, (b) independent of Na'-H' exchange activity, and (c) not due to changes in transepithelial fluxes of total ammonia. These results suggest that luminal potassium concentration has a direct effect on cell-to-lumen transport of ammonia. (J. Clin. Invest. 1990. 86:32-39.)

Effect of angiotensin II on ammonia production and secretion by mouse proximal tubules perfused in vitro.

“…The countervailing effects of angiotensin II on production and transport of tNH3 may be important in limiting the effect of angiotensin II on overall acid-base balance. We have observed similar counteracting effects of luminal and bath potassium concentrations on tNH3 production and secretion in mouse proximal tubules (13). The opposing effects ofangiotensin II on tNH3 production and secretion rates represent another example of the dissociation between tNH3 production and transport in the proxiial tubule.…”

“…In previous studies, we have used the isolated perfused mouse proximal tubule segment to examine the effects ofacute changes in luminal flow rates, pH, and potassium concentration in vitro on ammonia production and transport (1 [1][2][3][4][5][6][7][8][9][10][11][12][13] 02:5% C02. The tubule was incubated for 20-30 min at 370C.…”

Mechanisms in Hyperkalemic Renal Tubular Acidosis

“…Isolated perfused mouse nephrons yielded similar findings: a significant fall in proximal tubular ammonia production without affecting the rate of secretion. 30 Despite agreement that proximal production is affected, how this is achieved is unclear. It probably involves potassium entry into cells, displacing protons and thereby raising intracellular pH, 31,32 which by extrapolation from the opposite effects of acidosis likely leads to reduced enzyme function ( Figure 1B); however, a number of unresolved issues remain.…”

Molecular Mechanisms of Renal Ammonia Transport

“…These include augmented proximal tubule ammoniagenesis, which involves increases in the following: activity and expression of key ammoniagenic enzymes (9,23) The regulation of proximal tubule apical NHE-3 is important in the regulation of proximal tubule ammonia transport. Chronic metabolic acidosis, changes in extracellular K + , and angiotensin II (AII) regulate proximal tubule ammonia secretion, apparently through changes in apical Na + /H + exchange activity (25,30). In chronic metabolic acidosis and hypokalemia, parallel changes in NHE-3 expression were observed (26,31).…”