Abstract
Rat inner medullary collecting ducts (IMCD3s) possess a luminal Na+-dependent, active urea secretory transport process, which is upregulated by water diuresis. In this study of perfused IMCDs microdissected from base (IMCD1), middle (IMCD2), or tip (IMCD3) of the inner medulla, we tested whether furosemide diuresis alters active urea transport. Rats received furosemide (10 mg/d s.c. for 3-4 d) and were compared with pair-fed control rats. Furosemide significantly decreased urine osmolality and urea clearance, and increased blood urea nitrogen. IMCD3s from furosemide-treated rats had significantly lower rates of active urea secretion than IMCD3s from control rats. IMCD2s showed no active urea transport in control or furosemide-treated rats. IMCD1s from control rats had no active urea transport, but IMCD1s from furosemide-treated rats expressed significant rates of active urea reabsorption. In IMCD1s, this active urea reabsorptive transport process was inhibited by: (i) 0. 25 mM phloretin (bath); (ii) 1 mM ouabain (bath); and (iii) replacing bath Na+ with NMDG+; it was stimulated by 10 nM bumetanide (bath). In summary, we found that furosemide decreased active urea secretion in IMCD3s and induced active urea reabsorption in IMCD1s. The new Na+- dependent, active urea reabsorptive transport process may be a basolateral Na+-urea antiporter.
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- Beyer K. H., Jr, Gelarden R. T. Active transport of urea by mammalian kidney. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4030–4031. doi: 10.1073/pnas.85.11.4030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beyer K. H., Jr, Gelarden R. T., Vary J. E., Brown L. E., Vesell E. S. Novel multivalent effects of pyrazinoylguanidine in patients with azotemia. Clin Pharmacol Ther. 1990 May;47(5):629–638. doi: 10.1038/clpt.1990.84. [DOI] [PubMed] [Google Scholar]
- Beyer K. H., Jr, Gelarden R. T., Vesell E. S. Inhibition of urea transport across renal tubules by pyrazinoylguanidine and analogs. Pharmacology. 1992;44(3):124–138. doi: 10.1159/000138905. [DOI] [PubMed] [Google Scholar]
- Biemesderfer D., Payne J. A., Lytle C. Y., Forbush B., 3rd Immunocytochemical studies of the Na-K-Cl cotransporter of shark kidney. Am J Physiol. 1996 Jun;270(6 Pt 2):F927–F936. doi: 10.1152/ajprenal.1996.270.6.F927. [DOI] [PubMed] [Google Scholar]
- Burg M. B., Green N. Function of the thick ascending limb of Henle's loop. Am J Physiol. 1973 Mar;224(3):659–668. doi: 10.1152/ajplegacy.1973.224.3.659. [DOI] [PubMed] [Google Scholar]
- Burg M., Green N. Effect of ethacrynic acid on the thick ascending limb of Henle's loop. Kidney Int. 1973 Nov;4(5):301–308. doi: 10.1038/ki.1973.121. [DOI] [PubMed] [Google Scholar]
- Clapp W. L., Madsen K. M., Verlander J. W., Tisher C. C. Intercalated cells of the rat inner medullary collecting duct. Kidney Int. 1987 May;31(5):1080–1087. doi: 10.1038/ki.1987.111. [DOI] [PubMed] [Google Scholar]
- Clapp W. L., Madsen K. M., Verlander J. W., Tisher C. C. Morphologic heterogeneity along the rat inner medullary collecting duct. Lab Invest. 1989 Feb;60(2):219–230. [PubMed] [Google Scholar]
- Dal Canton A., Fuiano G., Conte G., Terribile M., Sabbatini M., Cianciaruso B., Andreucci V. E. Mechanism of increased plasma urea after diuretic therapy in uraemic patients. Clin Sci (Lond) 1985 Mar;68(3):255–261. doi: 10.1042/cs0680255. [DOI] [PubMed] [Google Scholar]
- Delpire E., Rauchman M. I., Beier D. R., Hebert S. C., Gullans S. R. Molecular cloning and chromosome localization of a putative basolateral Na(+)-K(+)-2Cl- cotransporter from mouse inner medullary collecting duct (mIMCD-3) cells. J Biol Chem. 1994 Oct 14;269(41):25677–25683. [PubMed] [Google Scholar]
- Ecelbarger C. A., Terris J., Hoyer J. R., Nielsen S., Wade J. B., Knepper M. A. Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1. Am J Physiol. 1996 Sep;271(3 Pt 2):F619–F628. doi: 10.1152/ajprenal.1996.271.3.F619. [DOI] [PubMed] [Google Scholar]
- Ginns S. M., Knepper M. A., Ecelbarger C. A., Terris J., He X., Coleman R. A., Wade J. B. Immunolocalization of the secretory isoform of Na-K-Cl cotransporter in rat renal intercalated cells. J Am Soc Nephrol. 1996 Dec;7(12):2533–2542. doi: 10.1681/ASN.V7122533. [DOI] [PubMed] [Google Scholar]
- Goldberg M., Wojtczak A. M., Ramirez M. A. Uphill transport of urea in the dog kidney: effects of certain inhibitors. J Clin Invest. 1967 Mar;46(3):388–399. doi: 10.1172/JCI105540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grunewald J. M., Grunewald R. W., Kinne R. K. Ion content and cell volume in isolated collecting duct cells: effect of hypotonicity. Kidney Int. 1993 Sep;44(3):509–517. doi: 10.1038/ki.1993.275. [DOI] [PubMed] [Google Scholar]
- Grupp C., Pavenstädt-Grupp I., Grunewald R. W., Bevan C., Stokes J. B., 3rd, Kinne R. K. A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells. Kidney Int. 1989 Aug;36(2):201–209. doi: 10.1038/ki.1989.180. [DOI] [PubMed] [Google Scholar]
- Han J. S., Thompson K. A., Chou C. L., Knepper M. A. Experimental tests of three-dimensional model of urinary concentrating mechanism. J Am Soc Nephrol. 1992 Jun;2(12):1677–1688. doi: 10.1681/ASN.V2121677. [DOI] [PubMed] [Google Scholar]
- Hering-Smith K. S., Cragoe E. J., Jr, Weiner D., Hamm L. L. Inner medullary collecting duct Na(+)-H+ exchanger. Am J Physiol. 1991 Jun;260(6 Pt 1):C1300–C1307. doi: 10.1152/ajpcell.1991.260.6.C1300. [DOI] [PubMed] [Google Scholar]
- Hsu C. H., Kurtz T. W., Massari P. U., Ponze S. A., Chang B. S. Familial azotemia. Impaired urea excretion despite normal renal function. N Engl J Med. 1978 Jan 19;298(3):117–121. doi: 10.1056/NEJM197801192980301. [DOI] [PubMed] [Google Scholar]
- Isozaki T., Gillin A. G., Swanson C. E., Sands J. M. Protein restriction sequentially induces new urea transport processes in rat initial IMCD. Am J Physiol. 1994 May;266(5 Pt 2):F756–F761. doi: 10.1152/ajprenal.1994.266.5.F756. [DOI] [PubMed] [Google Scholar]
- Isozaki T., Lea J. P., Tumlin J. A., Sands J. M. Sodium-dependent net urea transport in rat initial inner medullary collecting ducts. J Clin Invest. 1994 Oct;94(4):1513–1517. doi: 10.1172/JCI117491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isozaki T., Verlander J. W., Sands J. M. Low protein diet alters urea transport and cell structure in rat initial inner medullary collecting duct. J Clin Invest. 1993 Nov;92(5):2448–2457. doi: 10.1172/JCI116852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamm D. E., Wu L., Kuchmy B. L. Contribution of the urea appearance rate to diuretic-induced azotemia in the rat. Kidney Int. 1987 Jul;32(1):47–56. doi: 10.1038/ki.1987.170. [DOI] [PubMed] [Google Scholar]
- Kaplan M. R., Plotkin M. D., Brown D., Hebert S. C., Delpire E. Expression of the mouse Na-K-2Cl cotransporter, mBSC2, in the terminal inner medullary collecting duct, the glomerular and extraglomerular mesangium, and the glomerular afferent arteriole. J Clin Invest. 1996 Aug 1;98(3):723–730. doi: 10.1172/JCI118844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan M. R., Plotkin M. D., Lee W. S., Xu Z. C., Lytton J., Hebert S. C. Apical localization of the Na-K-Cl cotransporter, rBSC1, on rat thick ascending limbs. Kidney Int. 1996 Jan;49(1):40–47. doi: 10.1038/ki.1996.6. [DOI] [PubMed] [Google Scholar]
- Kato A., Naruse M., Knepper M. A., Sands J. M. Long-term regulation of inner medullary collecting duct urea transport in rat. J Am Soc Nephrol. 1998 May;9(5):737–745. doi: 10.1681/ASN.V95737. [DOI] [PubMed] [Google Scholar]
- Kato A., Sands J. M. Evidence for sodium-dependent active urea secretion in the deepest subsegment of the rat inner medullary collecting duct. J Clin Invest. 1998 Jan 15;101(2):423–428. doi: 10.1172/JCI1420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawamura S., Kokko J. P. Urea secretion by the straight segment of the proximal tubule. J Clin Invest. 1976 Sep;58(3):604–612. doi: 10.1172/JCI108507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly R. A., Wilcox C. S., Mitch W. E., Meyer T. W., Souney P. F., Rayment C. M., Friedman P. A., Swartz S. L. Response of the kidney to furosemide. II. Effect of captopril on sodium balance. Kidney Int. 1983 Aug;24(2):233–239. doi: 10.1038/ki.1983.149. [DOI] [PubMed] [Google Scholar]
- Nielsen S., Terris J., Smith C. P., Hediger M. A., Ecelbarger C. A., Knepper M. A. Cellular and subcellular localization of the vasopressin- regulated urea transporter in rat kidney. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5495–5500. doi: 10.1073/pnas.93.11.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sands J. M., Knepper M. A. Urea permeability of mammalian inner medullary collecting duct system and papillary surface epithelium. J Clin Invest. 1987 Jan;79(1):138–147. doi: 10.1172/JCI112774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sands J. M., Nonoguchi H., Knepper M. A. Vasopressin effects on urea and H2O transport in inner medullary collecting duct subsegments. Am J Physiol. 1987 Nov;253(5 Pt 2):F823–F832. doi: 10.1152/ajprenal.1987.253.5.F823. [DOI] [PubMed] [Google Scholar]
- Sands J. M., Timmer R. T., Gunn R. B. Urea transporters in kidney and erythrocytes. Am J Physiol. 1997 Sep;273(3 Pt 2):F321–F339. doi: 10.1152/ajprenal.1997.273.3.F321. [DOI] [PubMed] [Google Scholar]
- Schmidt-Nielsen B., Truniger B., Rabinowitz L. Sodium-linked urea transport by the renal tubule of the spiny dogfish Squalus acanthias. Comp Biochem Physiol A Comp Physiol. 1972 May 1;42(1):13–25. doi: 10.1016/0300-9629(72)90360-x. [DOI] [PubMed] [Google Scholar]
- Shayakul C., Steel A., Hediger M. A. Molecular cloning and characterization of the vasopressin-regulated urea transporter of rat kidney collecting ducts. J Clin Invest. 1996 Dec 1;98(11):2580–2587. doi: 10.1172/JCI119077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soybel D. I., Gullans S. R., Maxwell F., Delpire E. Role of basolateral Na(+)-K(+)-Cl- cotransport in HCl secretion by amphibian gastric mucosa. Am J Physiol. 1995 Jul;269(1 Pt 1):C242–C249. doi: 10.1152/ajpcell.1995.269.1.C242. [DOI] [PubMed] [Google Scholar]
- Sun A., Hebert S. C. Rapid hypertonic cell volume regulation in the perfused inner medullary collecting duct. Kidney Int. 1989 Nov;36(5):831–842. doi: 10.1038/ki.1989.269. [DOI] [PubMed] [Google Scholar]
- Terris J., Ecelbarger C. A., Sands J. M., Knepper M. A. Long-term regulation of renal urea transporter protein expression in rat. J Am Soc Nephrol. 1998 May;9(5):729–736. doi: 10.1681/ASN.V95729. [DOI] [PubMed] [Google Scholar]
- Wexler A. S., Kalaba R. E., Marsh D. J. Three-dimensional anatomy and renal concentrating mechanism. I. Modeling results. Am J Physiol. 1991 Mar;260(3 Pt 2):F368–F383. doi: 10.1152/ajprenal.1991.260.3.F368. [DOI] [PubMed] [Google Scholar]
- Wilcox C. S., Guzman N. J., Mitch W. E., Kelly R. A., Maroni B. J., Souney P. F., Rayment C. M., Braun L., Colucci R., Loon N. R. Na+, K+, and BP homeostasis in man during furosemide: effects of prazosin and captopril. Kidney Int. 1987 Jan;31(1):135–141. doi: 10.1038/ki.1987.20. [DOI] [PubMed] [Google Scholar]
- Wilcox C. S., Mitch W. E., Kelly R. A., Skorecki K., Meyer T. W., Friedman P. A., Souney P. F. Response of the kidney to furosemide. I. Effects of salt intake and renal compensation. J Lab Clin Med. 1983 Sep;102(3):450–458. [PubMed] [Google Scholar]
- Yang T., Huang Y. G., Singh I., Schnermann J., Briggs J. P. Localization of bumetanide- and thiazide-sensitive Na-K-Cl cotransporters along the rat nephron. Am J Physiol. 1996 Oct;271(4 Pt 2):F931–F939. doi: 10.1152/ajprenal.1996.271.4.F931. [DOI] [PubMed] [Google Scholar]