Abstract
These studies examine the inhibitory effects of arsenate on the transport of sodium, phosphate, glucose, and para-aminohippurate (PAH) as well as oxidative metabolism by proximal convoluted tubules from the rabbit kidney. Transport rates were measured with radioisotopes in isolated and perfused segments. Metabolic activity was monitored through oxygen-consumption rates and HADH fluorescence in parallel studies in suspensions of cortical tubules. The addition of 1mM arsenate to the perfusate reduced fluid absorption rates from 1.24 +/- 0.17 to 0.66 +/- 0.19 nl/nm.min (P < 0.01) and lumen-to-bath phosphate transport from 9.93 +/- 3.47 to 4.25 +/- 1.08 pmol/mm.min (P < 0.01). Similar concentrations of arsenate reduced glucose transport only slightly from 66.1 +/- 6.0 to 56.8 +/-4 4.6 pmol/mm.min (P < 0.05) and had no effect of PAH secretion. Removing phosphate from the perfusate did not affect the net transport of sodium or glucose. In suspensions of tubules, arsenate increased oxygen consumption rates by 20.5 +/- 2.9% and decreased NADH fluorescence by 10.8 +/- 1.5%. These effects on metabolism were concentration dependent and magnified in the presence of ouabain. The data indicate that arsenate's main effect is to uncouple oxidative phosphorylation, and that graded uncoupling of oxidative metabolism causes graded reductions in the net transport of both sodium and phosphate. Glucose transport is inhibited only slightly and PAH secretion is not affected. Thus, partial as opposed to complete inhibition of metabolism reveals that different relationships exist between net sodium transport and the transport of phosphate, glucose, and PAH by the proximal renal tubule.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Balaban R. S., Mandel L. J., Soltoff S. P., Storey J. M. Coupling of active ion transport and aerobic respiratory rate in isolated renal tubules. Proc Natl Acad Sci U S A. 1980 Jan;77(1):447–451. doi: 10.1073/pnas.77.1.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Balaban R. S., Soltoff S. P., Storey J. M., Mandel L. J. Improved renal cortical tubule suspension: spectrophotometric study of O2 delivery. Am J Physiol. 1980 Jan;238(1):F50–F59. doi: 10.1152/ajprenal.1980.238.1.F50. [DOI] [PubMed] [Google Scholar]
- Baumann K., de Rouffignac C., Roinel N., Rumrich G., Ullrich K. J. Renal phosphate transport: inhomogeneity of local proximal transport rates and sodium dependence. Pflugers Arch. 1975;356(4):287–298. doi: 10.1007/BF00580003. [DOI] [PubMed] [Google Scholar]
- Beck J. C., Sacktor B. Membrane potential-sensitive fluorescence changes during Na+-dependent D-glucose transport in renal brush border membrane vesicles. J Biol Chem. 1978 Oct 25;253(20):7158–7162. [PubMed] [Google Scholar]
- Beck J. C., Sacktor B. The sodium electrochemical potential-mediated uphill transport of D-glucose in renal brush border membrane vesicles. J Biol Chem. 1978 Aug 10;253(15):5531–5535. [PubMed] [Google Scholar]
- Berner W., Kinne R. Transport of p-aminohippuric acid by plasma membrane vesicles isolated from rat kidney cortex. Pflugers Arch. 1976 Feb 24;361(3):269–277. doi: 10.1007/BF00587292. [DOI] [PubMed] [Google Scholar]
- Brazy P. C., Dennis V. W. Characteristics of glucose-phlorizin interactions in isolated proximal tubules. Am J Physiol. 1978 Apr;234(4):F279–F286. doi: 10.1152/ajprenal.1978.234.4.F279. [DOI] [PubMed] [Google Scholar]
- Burg M., Patlak C., Green N., Villey D. Organic solutes in fluid absorption by renal proximal convoluted tubules. Am J Physiol. 1976 Aug;231(2):627–637. doi: 10.1152/ajplegacy.1976.231.2.627. [DOI] [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956;17:65–134. doi: 10.1002/9780470122624.ch2. [DOI] [PubMed] [Google Scholar]
- CRANE R. K., LIPMANN F. The effect of arsenate on aerobic phosphorylation. J Biol Chem. 1953 Mar;201(1):235–243. [PubMed] [Google Scholar]
- Chapman J. B. Fluorometric studies of oxidative metabolism in isolated papillary muscle of the rabbit. J Gen Physiol. 1972 Feb;59(2):135–154. doi: 10.1085/jgp.59.2.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen R. F. Removal of fatty acids from serum albumin by charcoal treatment. J Biol Chem. 1967 Jan 25;242(2):173–181. [PubMed] [Google Scholar]
- Dennis V. W., Brazy P. C. Sodium, phosphate, glucose, bicarbonate, and alanine interactions in the isolated proximal convoluted tubule of the rabbit kidney. J Clin Invest. 1978 Aug;62(2):387–397. doi: 10.1172/JCI109140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dennis V. W., Woodhall P. B., Robinson R. R. Characteristics of phosphate transport in isolated proximal tubule. Am J Physiol. 1976 Sep;231(3):979–985. doi: 10.1152/ajplegacy.1976.231.3.979. [DOI] [PubMed] [Google Scholar]
- GINSBURG J. M., LOTSPEICH W. D. INTERRELATIONS OF ARSENATE AND PHOSPHATE TRANSPORT IN THE DOG KIDNEY. Am J Physiol. 1963 Oct;205:707–714. doi: 10.1152/ajplegacy.1963.205.4.707. [DOI] [PubMed] [Google Scholar]
- GINSBURG J. M. RENAL MECHANISM FOR EXCRETION AND TRANSFORMATION OF ARSENIC IN THE DOG. Am J Physiol. 1965 May;208:832–840. doi: 10.1152/ajplegacy.1965.208.5.832. [DOI] [PubMed] [Google Scholar]
- GOLDSBY R. A., HEYTLER P. G. UNCOUPLING OF OXIDATIVE PHOSPHORYLATION BY CARBONYL CYANIDE PHENYLHYDRAZONES. II. EFFECTS OF CARBONYL CYANIDE M-CHLOROPHENYLHYDRAZONE ON MITOCHONDRIAL RESPIRATION. Biochemistry. 1963 Sep-Oct;2:1142–1147. doi: 10.1021/bi00905a041. [DOI] [PubMed] [Google Scholar]
- Györy A. Z., Kinne R. Energy source for transepithelial sodium transport in rat renal proximal tubules. Pflugers Arch. 1971;327(3):234–260. doi: 10.1007/BF00586861. [DOI] [PubMed] [Google Scholar]
- Harold F. M., Spitz E. Accumulation of arsenate, phosphate, and aspartate by Sreptococcus faecalis. J Bacteriol. 1975 Apr;122(1):266–277. doi: 10.1128/jb.122.1.266-277.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hernandez J., Capek K., Heller J., Nováková A. The effect of uncouplers of oxidative phosphorylation on sodium transport in the proximal renal tubule of the rat. Experientia. 1969 Feb 15;25(2):125–125. doi: 10.1007/BF01899075. [DOI] [PubMed] [Google Scholar]
- Hoffmann N., Thees M., Kinne R. Phosphate transport by isolated renal brush border vesicles. Pflugers Arch. 1976 Mar 30;362(2):147–156. doi: 10.1007/BF00583641. [DOI] [PubMed] [Google Scholar]
- Jöbsis F. F., Duffield J. C. Oxidative and glycolytic recovery metabolism in muscle. J Gen Physiol. 1967 Mar;50(4):1009–1047. doi: 10.1085/jgp.50.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knox F. G., Fleming J. S., Rennie D. W. Effects of osmotic diuresis on sodium reabsorption and oxygen consumption of kidney. Am J Physiol. 1966 Apr;210(4):751–759. doi: 10.1152/ajplegacy.1966.210.4.751. [DOI] [PubMed] [Google Scholar]
- Kokko J. P., Burg M. B., Orloff J. Characteristics of NaCl and water transport in the renal proximal tubule. J Clin Invest. 1971 Jan;50(1):69–76. doi: 10.1172/JCI106485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Levinson C. Phosphate transport in Ehrlich ascites tumor cells and the effect of arsenate. J Cell Physiol. 1972 Feb;79(1):73–77. doi: 10.1002/jcp.1040790108. [DOI] [PubMed] [Google Scholar]
- Needham D. M., Pillai R. K. The coupling of oxido-reductions and dismutations with esterification of phosphate in muscle. Biochem J. 1937 Oct;31(10):1837–1851. doi: 10.1042/bj0311837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Podevin R. A., Boumendil-Podevin E. F., Priol C. Concentrative PAH transport by rabbit kidney slices in the absence of metabolic energy. Am J Physiol. 1978 Oct;235(4):F278–F285. doi: 10.1152/ajprenal.1978.235.4.F278. [DOI] [PubMed] [Google Scholar]
- ROTHSTEIN A. Interactions of arsenate with the phosphate-transporting system of yeast. J Gen Physiol. 1963 May;46:1075–1085. doi: 10.1085/jgp.46.5.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs G. Ion pumps in the renal tubule. Am J Physiol. 1977 Nov;233(5):F359–F365. doi: 10.1152/ajprenal.1977.233.5.F359. [DOI] [PubMed] [Google Scholar]
- Schafer J. A., Troutman S. L., Andreoli T. E. Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules. J Gen Physiol. 1974 Nov;64(5):582–607. doi: 10.1085/jgp.64.5.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simpson D. P., Hecker J. Effect of arsenite on renal tissue slice metabolism in chronic metabolic acidosis and alkalosis. Am J Physiol. 1979 Aug;237(2):F93–F99. doi: 10.1152/ajprenal.1979.237.2.F93. [DOI] [PubMed] [Google Scholar]
- Tune B. M., Burg M. B. Glucose transport by proximal renal tubules. Am J Physiol. 1971 Aug;221(2):580–585. doi: 10.1152/ajplegacy.1971.221.2.580. [DOI] [PubMed] [Google Scholar]
- Ullrich K. J., Rumrich G., Klöss S. Specificity and sodium dependence of the active sugar transport in the proximal convolution of the rat kidney. Pflugers Arch. 1974;351(1):35–48. doi: 10.1007/BF00603509. [DOI] [PubMed] [Google Scholar]
- WINDHAGER E. E., GIEBISCH G. Comparison of short-circuit current and net water movement in single perfused proximal tubules of rat kidneys. Nature. 1961 Sep 16;191:1205–1207. doi: 10.1038/1911205a0. [DOI] [PubMed] [Google Scholar]
- Wilson D. F., Erecińska M., Drown C., Silver I. A. Effect of oxygen tension on cellular energetics. Am J Physiol. 1977 Nov;233(5):C135–C140. doi: 10.1152/ajpcell.1977.233.5.C135. [DOI] [PubMed] [Google Scholar]