Mechanism of acidification along cortical distal tubule of the rat.
The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.
Fernandez
R
R
Department of Physiology and Biophysics, University of São Paulo, Brazil.
Lopes
M J
MJ
de Lira
R F
RF
Dantas
W F
WF
Cragoe Júnior
E J
EJ
Malnic
G
G
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000502:physiology* / Q000503:physiopathology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D007700:Kinetics; D018942:Macrolides; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010477:Perfusion / Q000295:instrumentation / Q000379:methods; D011191:Potassium Deficiency / Q000503:physiopathology; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001639:Bicarbonates; D007093:Imidazoles; D018942:Macrolides; D054328:Proton Pump Inhibitors; C035235:Sch 28080; C013407:benzamil; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases