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AJP - Renal Physiology, Vol 270, Issue 4 691-F699, Copyright © 1996 by American Physiological Society
ARTICLES |
D. W. Good and B. A. Watts 3rd
Department of Medicine, University of Texas Medical Branch, Galveston 77555, USA.
The medullary thick ascending limb (MTAL) of the rat actively absorbs both HCO3- and ammonium. The roles of apical membranes Na+/H+ exchange in these processes and in determining steady-state intracellular pH (pHi) were examined in MTAL perfused in vitro with solutions containing 146 mM Na+ and 25 mM HCO3- (pH 7.4). Addition of 1 mM amiloride or 50 microM ethylisopropylamiloride (EIPA) to the lumen decreased HCO3- absorption (JHCO3) from 10.6 +/- 0.5 to 2.3 +/- 0.3 pmol.min-1.mm-1 (P < 0.001) and pHi from 7.10 +/- 0.02 to 6.86 +/- 0.03 (P < 0.001). The combination of lumen Na+ replacement plus amiloride abolished JHCO3. Chronic metabolic acidosis (CMA) caused a 32% increase in JHCO3 that was inhibited by luminal amiloride. Addition of 4 mM NH4Cl to perfusate and bath markedly decreased pHi (from 7.10 to 6.70) but did not stimulate luminal H+ secretion as assessed by HCO3- absorption. With 4 mM NH4Cl in perfusate and bath, luminal addition of amiloride decreased pHi from 6.70 +/- 0.06 to 6.50 +/- 0.05 (P < 0.005) but had no effect on net ammonium absorption. These results demonstrate that 1) apical membrane Na+/H+ exchange mediates virtually all of HCO3- absorption and is an important determinant of steady-state pHi in the MTAL; 2) the adaptive increase in HCO3- absorption in CMA is mediated by an increase in apical membrane Na+/H+ exchange; 3) ammonium markedly acidifies the cells but does not stimulate luminal acidification, suggesting that pHi is not a predominant influence on apical Na+/H+ exchange activity and that H+ generated in the cells as the result of transcellular ammonium absorption is extruded across the basolateral membrane; and 4) apical membrane Na+/H+ exchange is not important for ammonium absorption.
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  B. A. Watts III, T. George, and D. W. Good Aldosterone inhibits apical NHE3 and HCO3- absorption via a nongenomic ERK-dependent pathway in medullary thick ascending limb Am J Physiol Renal Physiol, November 1, 2006; 291(5): F1005 - F1013. [Abstract] [Full Text] [PDF]
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M. Herrera, P. A. Ortiz, and J. L. Garvin Regulation of thick ascending limb transport: role of nitric oxide Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1279 - F1284. [Abstract] [Full Text] [PDF]
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 R. Juncos, N. J. Hong, and J. L. Garvin Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in the thick ascending limb Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R79 - R83. [Abstract] [Full Text] [PDF]
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 A. K. Rad, R. J. Balment, and N. Ashton Rapid natriuretic action of aldosterone in the rat J Appl Physiol, February 1, 2005; 98(2): 423 - 428. [Abstract] [Full Text] [PDF]
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D. W. Good, B. A. Watts III, T. George, J. W. Meyer, and G. E. Shull Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1244 - F1249. [Abstract] [Full Text] [PDF]
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B. A. Watts III and D. W. Good An apical K+-dependent HCO3- transport pathway opposes transepithelial HCO3- absorption in rat medullary thick ascending limb Am J Physiol Renal Physiol, July 1, 2004; 287(1): F57 - F63. [Abstract] [Full Text] [PDF]
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D. W. Good, T. George, and B. A. Watts III Aldosterone potentiates 1,25-dihydroxyvitamin D3 action in renal thick ascending limb via a nongenomic, ERK-dependent pathway Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1122 - C1130. [Abstract] [Full Text] [PDF]
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T.-H. Kwon, J. Nielsen, Y.-H. Kim, M. A. Knepper, J. Frokiaer, and S. Nielsen Regulation of sodium transporters in the thick ascending limb of rat kidney: response to angiotensin II Am J Physiol Renal Physiol, July 1, 2003; 285(1): F152 - F165. [Abstract] [Full Text] [PDF]
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D. W. Good, T. George, and B. A. Watts III Aldosterone inhibits HCO-3 absorption via a nongenomic pathway in medullary thick ascending limb Am J Physiol Renal Physiol, October 1, 2002; 283(4): F699 - F706. [Abstract] [Full Text] [PDF]
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P. A. Ortiz and J. L. Garvin Role of nitric oxide in the regulation of nephron transport Am J Physiol Renal Physiol, May 1, 2002; 282(5): F777 - F784. [Abstract] [Full Text] [PDF]
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S. Bourgeois, S. Masse, M. Paillard, and P. Houillier Basolateral membrane Cl--, Na+-, and K+-coupled base transport mechanisms in rat MTALH Am J Physiol Renal Physiol, April 1, 2002; 282(4): F655 - F668. [Abstract] [Full Text] [PDF]
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T. Wang, M. Hropot, P. S. Aronson, and G. Giebisch Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1117 - F1122. [Abstract] [Full Text] [PDF]
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A. Attmane-Elakeb, H. Amlal, and M. Bichara Ammonium carriers in medullary thick ascending limb Am J Physiol Renal Physiol, January 1, 2001; 280(1): F1 - F9. [Abstract] [Full Text] [PDF]
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D. W. Good, J. F. Di Mari, and B. A. Watts III Hyposmolality stimulates Na+/H+ exchange and HCO3- absorption in thick ascending limb via PI 3-kinase Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1443 - C1454. [Abstract] [Full Text] [PDF]
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H. Amlal, K. Habo, and M. Soleimani Potassium deprivation upregulates expression of renal basolateral Na+-HCO3- cotransporter (NBC-1) Am J Physiol Renal Physiol, September 1, 2000; 279(3): F532 - F543. [Abstract] [Full Text] [PDF]
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 G.-H. KIM, C. ECELBARGER, M. A. KNEPPER, and R. K. PACKER Regulation of Thick Ascending Limb Ion Transporter Abundance in Response to Altered Acid/Base Intake J. Am. Soc. Nephrol., May 1, 1999; 10(5): 935 - 942. [Abstract] [Full Text]
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D. W. Good, T. George, and D. H. Wang Angiotensin II inhibits HCO-3 absorption via a cytochrome P-450-dependent pathway in MTAL Am J Physiol Renal Physiol, May 1, 1999; 276(5): F726 - F736. [Abstract] [Full Text] [PDF]
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 B. A. Watts III, T. George, and D. W. Good Nerve Growth Factor Inhibits HCO3- Absorption in Renal Thick Ascending Limb through Inhibition of Basolateral Membrane Na+/H+ Exchange J. Biol. Chem., March 19, 1999; 274(12): 7841 - 7847. [Abstract] [Full Text] [PDF]
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B. A. Watts III, J. F. Di Mari, R. J. Davis, and D. W. Good Hypertonicity activates MAP kinases and inhibits HCO-3 absorption via distinct pathways in thick ascending limb Am J Physiol Renal Physiol, October 1, 1998; 275(4): F478 - F486. [Abstract] [Full Text] [PDF]
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D. W. Good Nerve growth factor regulates HCO-3 absorption in thick ascending limb: modifying effects of vasopressin Am J Physiol Cell Physiol, April 1, 1998; 274(4): C931 - C939. [Abstract] [Full Text] [PDF]
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