Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Jan;50(1):35–48. doi: 10.1172/JCI106482

Urate-2-14C transport in the rat nephron

Ronald A Kramp 1, William E Lassiter 1, Carl W Gottschalk 1
PMCID: PMC291891  PMID: 5543881

Abstract

Intrarenal transport of urate-2-14C was studied in anesthetized rats using the microinjection technic. During saline diuresis, small volumes of urate-2-14C (0.24-0.48 mM) and inulin-3H were injected into surface proximal and distal convoluted tubules, and ureteral urine was collected serially. Total (74-96%) and direct (57-84%) urate recovery increased significantly the more distal the puncture site. Delayed recovery (±20%) remained approximately the same regardless of localization of the microinjection. After proximal injections, total and direct recoveries of urate-2-14C were significantly higher in rats treated with probenecid, pyrazinoate, or PAH than during saline diuresis alone, while the excretion rates were comparable after distal injection. Delayed recovery was not altered by drug administration. The decreased proximal reabsorption of urate is presumably due to an effect of the drugs on the luminal membrane of the nephron. For perfusion at high urate concentrations, nonradioactive urate was added to the injectate (0.89-1.78 mM). Urate-2-14C recovery was almost complete and there was no delayed excretion, demonstrating saturation kinetics. These findings are compatible with a carrier-mediated mechanism for urate transport probably located at the luminal border of the proximal tubular epithelium. No definitive evidence for urate secretion was found in these studies.

Full text

PDF
35

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arrizurieta-Muchnik E. E., Lassiter W. E., Lipham E. M., Gottschalk C. W. Micropuncture study of glomerulotubular balance in the rat kidney. Nephron. 1969;6(3):418–436. doi: 10.1159/000179743. [DOI] [PubMed] [Google Scholar]
  2. BEECHWOOD E. C., BERNDT W. O., MUDGE G. H. STOP-FLOW ANALYSIS OF TUBULAR TRANSPORT OF URIC ACID IN RABBITS. Am J Physiol. 1964 Dec;207:1265–1272. doi: 10.1152/ajplegacy.1964.207.6.1265. [DOI] [PubMed] [Google Scholar]
  3. BERLINER R. W., HILTON J. G., YU T. F., KENNEDY T. J. The renal mechanism for urate excretion in man. J Clin Invest. 1950 Apr;29(4):396–401. doi: 10.1172/JCI102271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baines A. D., Gottschalk C. W., Lassiter W. E. Microinjection study of p-aminohippurate excretion by rat kidneys. Am J Physiol. 1968 Apr;214(4):703–709. doi: 10.1152/ajplegacy.1968.214.4.703. [DOI] [PubMed] [Google Scholar]
  5. Biber T. U., Mylle M., Baines A. D., Gottschalk C. W., Oliver J. R., MacDowell M. C. A study by micropuncture and microdissection of acute renal damage in rats. Am J Med. 1968 May;44(5):664–705. doi: 10.1016/0002-9343(68)90251-9. [DOI] [PubMed] [Google Scholar]
  6. CHINARD F. P., ENNS T. Relative renal excretion patterns of sodium ion, chloride ion, urea, water and glomerular substances. Am J Physiol. 1955 Aug;182(2):247–250. doi: 10.1152/ajplegacy.1955.182.2.247. [DOI] [PubMed] [Google Scholar]
  7. Cannon P. J., Svahn D. S., Demartini F. E. The influence of hypertonic saline infusions upon the fractional reabsorption of urate and other ions in normal and hypertensive man. Circulation. 1970 Jan;41(1):97–108. doi: 10.1161/01.cir.41.1.97. [DOI] [PubMed] [Google Scholar]
  8. Cannon P. J., Symchych P. S., Demartini F. E. The distribution of urate in human and primate kidney. Proc Soc Exp Biol Med. 1968 Oct;129(1):278–284. doi: 10.3181/00379727-129-33303. [DOI] [PubMed] [Google Scholar]
  9. Dantzler W. H. Effect of metabolic alkalosis and acidosis on tubular urate secretion in water snakes. Am J Physiol. 1968 Sep;215(3):747–751. doi: 10.1152/ajplegacy.1968.215.3.747. [DOI] [PubMed] [Google Scholar]
  10. EPSTEIN F. H., PIGEON G. EXPERIMENTAL URATE NEROPATHY: STUDIES OF THE DISTRIBUTION OF URATE IN RENAL TISSUE. Nephron. 1964;1:144–157. doi: 10.1159/000179328. [DOI] [PubMed] [Google Scholar]
  11. Fanelli G. M., Jr, Bohn D., Stafford S. Functional characteristics of renal urate transport in the Cebus monkey. Am J Physiol. 1970 Mar;218(3):627–636. doi: 10.1152/ajplegacy.1970.218.3.627. [DOI] [PubMed] [Google Scholar]
  12. GIEBISCH G., KLOSE R. M., WINDHAGER E. E. MICROPUNCTURE STUDY OF HYPERTONIC SODIUM CHLORIDE LOADING IN THE RAT. Am J Physiol. 1964 Apr;206:687–693. doi: 10.1152/ajplegacy.1964.206.4.687. [DOI] [PubMed] [Google Scholar]
  13. GOTTSCHALK C. W., MOREL F., MYLLE M. TRACER MICROINJECTION STUDIES OF RENAL TUBULAR PERMEABILITY. Am J Physiol. 1965 Jul;209:173–178. doi: 10.1152/ajplegacy.1965.209.1.173. [DOI] [PubMed] [Google Scholar]
  14. GOTTSCHALK C. W., MYLLE M. Micropuncture study of pressures in proximal tubules and peritubular capillaries of the rat kidney and their relation to ureteral and renal venous pressures. Am J Physiol. 1956 May;185(2):430–439. doi: 10.1152/ajplegacy.1956.185.2.430. [DOI] [PubMed] [Google Scholar]
  15. GUTMAN A. B., YU T. F. A three-component system for regulation of renal excretion of uric acid in man. Trans Assoc Am Physicians. 1961;74:353–365. [PubMed] [Google Scholar]
  16. GUTMAN A. B., YU T. F., BERGER L. Tubular secretion of urate in man. J Clin Invest. 1959 Oct;38:1778–1781. doi: 10.1172/JCI103956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KESSLER R. H., HIERHOLZER K., GURD R. S. Localization of urate transport in the nephron of mongrel and Dalmatian dog kidney. Am J Physiol. 1959 Sep;197:601–603. doi: 10.1152/ajplegacy.1959.197.3.601. [DOI] [PubMed] [Google Scholar]
  18. KINTER W. B. Renal tubular transport of diodrast-I 131 and PAH in Necturus: evidence for simultaneous reabsorption and secretion. Am J Physiol. 1959 May;196(5):1141–1149. doi: 10.1152/ajplegacy.1959.196.5.1141. [DOI] [PubMed] [Google Scholar]
  19. LASSITER W. E., GOTTSCHALK C. W., MYLLE M. Micropuncture study of net transtubular movement of water and urea in nondiuretic mammalian kidney. Am J Physiol. 1961 Jun;200:1139–1147. doi: 10.1152/ajplegacy.1961.200.6.1139. [DOI] [PubMed] [Google Scholar]
  20. LASSITER W. E., MYLLE M., GOTTSCHALK C. W. NET TRANSTUBULAR MOVEMENT OF WATER AND UREA IN SALINE DIURESIS. Am J Physiol. 1964 Apr;206:669–673. doi: 10.1152/ajplegacy.1964.206.4.669. [DOI] [PubMed] [Google Scholar]
  21. LASSITER W. E., MYLLE M., GOTTSCHALK C. W. NET TRANSTUBULAR MOVEMENT OF WATER AND UREA IN SALINE DIURESIS. Am J Physiol. 1964 Apr;206:669–673. doi: 10.1152/ajplegacy.1964.206.4.669. [DOI] [PubMed] [Google Scholar]
  22. MOREL F., MYLLE M., GOTTSCHALK C. W. TRACER MICROINJECTION STUDIES OF EFFECT OF ADH ON RENAL TUBULAR DIFFUSION OF WATER. Am J Physiol. 1965 Jul;209:179–187. doi: 10.1152/ajplegacy.1965.209.1.179. [DOI] [PubMed] [Google Scholar]
  23. Mudge G. H., Cucchi J., Platts M., O'Connell J. M., Berndt W. O. Renal excretion of uric acid in the dog. Am J Physiol. 1968 Aug;215(2):404–410. doi: 10.1152/ajplegacy.1968.215.2.404. [DOI] [PubMed] [Google Scholar]
  24. Mudge G. H., McAlary B., Berndt W. O. Renal transport of uric acid in the guinea pig. Am J Physiol. 1968 Apr;214(4):875–879. doi: 10.1152/ajplegacy.1968.214.4.875. [DOI] [PubMed] [Google Scholar]
  25. Oelert H., Baumann K., Gekle D. Permeabilitätsmessungen einiger schwacher organischer Säuren aus dem distalen Konvolut der Rattenniere. Pflugers Arch. 1969;307(3):178–189. doi: 10.1007/BF00592083. [DOI] [PubMed] [Google Scholar]
  26. Podevin R., Ardaillou R., Paillard F., Fontanelle J., Richet G. Etude chez l'homme de la cinétique d'apparition dans l'urine de l'acide urique 2 14C. Nephron. 1968;5(2):134–140. doi: 10.1159/000179623. [DOI] [PubMed] [Google Scholar]
  27. Podevin R., Paillard F., Hornych A., Ardaillou R., Fontanelle J., Richet G. Cinétique d'apparition dans l'urine de l'acide para-aminohippurique (P.A.H.) et de l'acide urique 2-14C chez l'homme. Effets de la benziodarone, de l'acide acétyl-salicylique et de la pyrazinamide. Rev Fr Etud Clin Biol. 1968 May;13(5):513–522. [PubMed] [Google Scholar]
  28. Purkerson M. L., Lubowitz H., White R. W., Bricker N. S. On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat. J Clin Invest. 1969 Sep;48(9):1754–1760. doi: 10.1172/JCI106141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robson A. M., Srivastava P. L., Bricker N. S. The influence of saline loading on renal glucose reabsorption in the rat. J Clin Invest. 1968 Feb;47(2):329–335. doi: 10.1172/JCI105728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ross C. R., Farah A. p-Aminohippurate and N-methylnicotinamide transport in dog renal slices--an evaluation of the counter-transport hypothesis. J Pharmacol Exp Ther. 1966 Feb;151(2):159–167. [PubMed] [Google Scholar]
  31. Sonnenberg H., Oelert H., Baumann K. Proximal tubular reabsorption of some organic acids in the rat kidney in vivo. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 Oct 12;286(2):171–180. doi: 10.1007/BF00363859. [DOI] [PubMed] [Google Scholar]
  32. Steele T. H. Evidence for altered renal urate reabsorption during changes in volume of the extracellular fluid. J Lab Clin Med. 1969 Aug;74(2):288–299. [PubMed] [Google Scholar]
  33. Steele T. H., Oppenheimer S. Factors affecting urate excretion following diuretic administration in man. Am J Med. 1969 Oct;47(4):564–574. doi: 10.1016/0002-9343(69)90187-9. [DOI] [PubMed] [Google Scholar]
  34. WEINER I. M., MUDGE G. H. RENAL TUBULAR MECHANISMS FOR EXCRETION OF ORGANIC ACIDS AND BASES. Am J Med. 1964 May;36:743–762. doi: 10.1016/0002-9343(64)90183-4. [DOI] [PubMed] [Google Scholar]
  35. Walser M. Mathematical aspects of renal function: the dependence of solute reabsorption on water reabsorption, and the mechanism of osmotic natriuresis. J Theor Biol. 1966 Feb;10(2):307–326. doi: 10.1016/0022-5193(66)90129-9. [DOI] [PubMed] [Google Scholar]
  36. YU T. F., BERGER L., KUPFER S., GUTMAN A. B. Tubular secretion of urate in the dog. Am J Physiol. 1960 Dec;199:1199–1204. doi: 10.1152/ajplegacy.1960.199.6.1199. [DOI] [PubMed] [Google Scholar]
  37. YU T. F., BERGER L., STONE D. J., WOLF J., GUTMAN A. B. Effect of pyrazinamide and pyrazinoic acid on urate clearance and other discrete renal functions. Proc Soc Exp Biol Med. 1957 Oct;96(1):264–267. doi: 10.3181/00379727-96-23450. [DOI] [PubMed] [Google Scholar]
  38. YU T. F., GUTMAN A. B. Paradoxical retention of uric acid by uricosuric drugs in low dosage. Proc Soc Exp Biol Med. 1955 Nov;90(2):542–547. doi: 10.3181/00379727-90-22094. [DOI] [PubMed] [Google Scholar]
  39. YU T. F., GUTMAN A. B. Study of the paradoxical effects of salicylate in low, intermediate and high dosage on the renal mechanisms for excretion of urate in man. J Clin Invest. 1959 Aug;38(8):1298–1315. doi: 10.1172/JCI103905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zins G. R., Weiner I. M. Bidirectional urate transport limited to the proximal tubule in dogs. Am J Physiol. 1968 Aug;215(2):411–422. doi: 10.1152/ajplegacy.1968.215.2.411. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES