Luminal acidification in K-replete OMCDi: inhibition of bicarbonate absorption by K removal and luminal Ba.
We have previously demonstrated that significant luminal acidification in the K-replete rabbit inner stripe of the outer medullary collecting duct (OMCDi) occurs via a renal H-K-adenosinetriphosphatase (H-K-ATPase) sensitive to several of the gastric H-K-ATPase inhibitors. To investigate further the mechanism of K-dependent luminal acidification in K-replete OMCDi, we examined the effects of luminal K removal, luminal addition of Ba in the presence and absence of luminal 5.0 nM bafilomycin A1 (BAF), and basolateral addition of Ba on net bicarbonate flux (JtCO2, pmol.mm-1.min-1) and transepithelial voltage (VT, mV). Removal of K from the perfusate inhibited JtCO2 by 74% (13.4 +/- 4.0 for control, 3.5 +/- 1.4 pmol.mm-1.min-1 for experimental, P < 0.05) and was statistically equivalent to the degree of inhibition previously observed under identical experimental conditions by either 10 microM Sch-28080 or 10 microM A-80915A. Approximately 50% inhibition of JtCO2 was observed following luminal application of 2.0 mM Ba2+, and the degree of inhibition was statistically equivalent regardless of whether BAF was present (12.2 +/- 2.7 for control, 6.0 +/- 1.4 pmol.mm-1.min-1 for 2.0 mM Ba2+, P < 0.05; 9.6 +/- 1.2 for control with 5 nM BAF, 5.7 +/- 1.3 pmol.mm-1.min-1 for 2.0 mM Ba2+ with 5 nM BAF, P < 0.05). Additionally, increasing the luminal concentration of Ba2+ from 2.0 to 4.0 mM resulted in no further inhibition of JtCO2 (8.5 +/- 1.7 for control, 3.9 +/- 1.3 pmol.mm-1.min-1 for 4.0 mM Ba2+, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Armitage
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FE
Department of Internal Medicine, University of Florida, Gainesville, USA.
Wingo
C S
CS
D000042:Absorption / Q000187:drug effects; D000143:Acids / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D004594:Electrophysiology; D004848:Epithelium / Q000502:physiology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000502:physiology; D018942:Macrolides; D009285:Naphthoquinones / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits
D000143:Acids; D000900:Anti-Bacterial Agents; D001639:Bicarbonates; D007093:Imidazoles; D018942:Macrolides; D009285:Naphthoquinones; C035235:Sch 28080; C057620:bafilomycin A; C071895:A 80915A; D001464:Barium; D011188:Potassium