Skip to main content
SpringerLink
Log in

Genes and Proteins of Urea Transporters

  • Chapter
  • First Online:
Book cover Urea Transporters

Part of the book series: Subcellular Biochemistry ((SCBI,volume 73))

Abstract

A urea transporter protein in the kidney was first proposed in 1987. The first urea transporter cDNA was cloned in 1993. The SLC14a urea transporter family contains two major subgroups: SLC14a1, the UT-B urea transporter originally isolated from erythrocytes; and SLC14a2, the UT-A group originally isolated from kidney inner medulla. Slc14a1, the human UT-B gene, arises from a single locus located on chromosome 18q12.1-q21.1, which is located close to Slc14a2. Slc14a1 includes 11 exons, with the coding region extending from exon 4 to exon 11, and is approximately 30 kb in length. The Slc14a2 gene is a very large gene with 24 exons, is approximately 300 kb in length, and encodes 6 different isoforms. Slc14a2 contains two promoter elements: promoter I is located in the typical position, upstream of exon 1, and drives the transcription of UT-A1, UT-A1b, UT-A3, UT-A3b, and UT-A4; while promoter II is located within intron 12 and drives the transcription of UT-A2 and UT-A2b. UT-A1 and UT-A3 are located in the inner medullary collecting duct, UT-A2 in the thin descending limb and liver, UT-A5 in testis, UT-A6 in colon, UT-B1 primarily in descending vasa recta and erythrocytes, and UT-B2 in rumen.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abdoun K, Stumpff F, Rabbani I, Martens H (2010) Modulation of urea transport across sheep rumen epithelium in vitro by SCFA and CO2. Am J Physiol Gastrointest Liver Physiol 298(2):G190–G202

    CAS  PubMed  Google Scholar 

  2. Acher R, Chauvet J, Chauvet MT, Rouille Y (1999) Unique evolution of neurohypophysial hormones in cartilaginous fishes: possible implications for urea-based osmoregulation. J Exp Zool 284(5):475–484

    CAS  PubMed  Google Scholar 

  3. Ashkar ZM, Martial S, Isozaki T, Price SR, Sands JM (1995) Urea transport in initial IMCD of rats fed a low-protein diet: functional properties and mRNA abundance. Am J Physiol Renal Physiol 268(6):F1218–F1223

    CAS  Google Scholar 

  4. Bagnasco SM (2006) The erythrocyte urea transporter UT-B. J Membrane Biol 212(2):133–138

    CAS  Google Scholar 

  5. Bagnasco SM, Peng T, Janech MG, Karakashian A, Sands JM (2001) Cloning and characterization of the human urea transporter UT-A1 and mapping of the human Slc14a2 gene. Am J Physiol Renal Physiol 281:F400–F406

    CAS  PubMed  Google Scholar 

  6. Bagnasco SM, Peng T, Nakayama Y, Sands JM (2000) Differential expression of individual UT-A urea transporter isoforms in rat kidney. J Am Soc Nephrol 11(11):1980–1986

    CAS  PubMed  Google Scholar 

  7. Bagnis C, Chapel S, Chiaroni J, Bailly P (2009) A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro. Transfusion 49(5):967–976

    CAS  PubMed  Google Scholar 

  8. Bankir L, Chen K, Yang B (2004) Lack of UT-B in vasa recta and red blood cells prevents urea-induced improvement of urinary concentrating ability. Am J Physiol Renal Physiol 286(1):F144–F151

    CAS  PubMed  Google Scholar 

  9. Berger UV, Tsukaguchi H, Hediger MA (1998) Distribution of mRNA for the facilitated urea transporter UT3 in the rat nervous system. Anat Embryol 197:405–414

    CAS  PubMed  Google Scholar 

  10. Birukawa N, Ando H, Goto M, Kanda N, Pastene LA, Urano A (2008) Molecular cloning of urea transporters from the kidneys of baleen and toothed whales. Comp Biochem Physiol B Biochem Mol Bio 149(2):227–235

    Google Scholar 

  11. Blount MA, Klein JD, Martin CF, Tchapyjnikov D, Sands JM (2007) Forskolin stimulates phosphorylation and membrane accumulation of UT-A3. Am J Physiol Renal Physiol 293(4):F1308–F1313

    CAS  PubMed  Google Scholar 

  12. Blount MA, Sim JH, Zhou R, Martin CF, Lu W, Sands JM, Klein JD (2010) The expression of transporters involved in urine concentration recover differently after ceasing lithium treatment. Am J Physiol Renal Physiol 298:F601–F608

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Bradford AD, Terris J, Ecelbarger CA, Klein JD, Sands JM, Chou C-L, Knepper MA (2001) 97 and 117 kDa forms of the collecting duct urea transporter UT-A1 are due to different states of glycosylation. Am J Physiol Renal Physiol 281(1):F133–F143

    CAS  PubMed  Google Scholar 

  14. Braun MH, Steele SL, Ekker M, Perry SF (2009) Nitrogen excretion in developing zebrafish (Danio rerio): a role for Rh proteins and urea transporters. Am J Physiol Renal Physiol 296(5):F994–F1005

    CAS  PubMed  Google Scholar 

  15. Braun MH, Steele SL, Perry SF (2009) The responses of zebrafish (Danio rerio) to high external ammonia and urea transporter inhibition: nitrogen excretion and expression of rhesus glycoproteins and urea transporter proteins. J Exp Biol 212(23):3846–3856

    CAS  PubMed  Google Scholar 

  16. Cartron JP, Ripoche P (1995) Urea transport and Kidd blood groups. Transfus Clin Biol 2(4):309–315

    CAS  PubMed  Google Scholar 

  17. Chen G, Fröhlich O, Yang Y, Klein JD, Sands JM (2006) Loss of N-linked glycosylation reduces urea transporter UT-A1 response to vasopressin. J Biol Chem 281(37):27436–27442

    CAS  PubMed  Google Scholar 

  18. Collins D, Winter DC, Hogan AM, Schirmer L, Baird AW, Stewart GS (2010) Differential protein abundance and function of UT-B transporters in human colon. Am J Physiol Gastrointest Liver Physiol 298(3):G345–G351

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Couriaud C, Ripoche P, Rousselet G (1996) Cloning and functional characterization of a rat urea transporter: Expression in the brain. Biochim Biophys Acta Gene Struct Expression 1309(3):197–199

    CAS  Google Scholar 

  20. Doran JJ, Klein JD, Kim Y-H, Smith TD, Kozlowski SD, Gunn RB, Sands JM (2006) Tissue distribution of UT-A and UT-B mRNA and protein in rat. Am J Physiol Regul Integr Comp Physiol 290(5):R1446–R1459

    CAS  PubMed  Google Scholar 

  21. Doran JJ, Timmer RT, Sands JM (1999) Accurate mRNA size determination in northern analysis using individual lane size markers. Biotechniques 27:280–282

    CAS  PubMed  Google Scholar 

  22. Duchesne R, Klein JD, Velotta JB, Doran JJ, Rouillard P, Roberts BR, McDonough AA, Sands JM (2001) UT-A urea transporter protein in heart: increased abundance during uremia, hypertension, and heart failure. Circ Res 89:139–145

    CAS  PubMed  Google Scholar 

  23. Fenton RA, Cooper GJ, Morris ID, Smith CP (2002) Coordinated expression of UT-A and UT-B urea transporters in rat testis. Am J Physiol Cell Physiol 282(6):C1492–C1501

    CAS  PubMed  Google Scholar 

  24. Fenton RA, Cottingham CA, Stewart GS, Howorth A, Hewitt JA, Smith CP (2002) Structure and characterization of the mouse UT-A gene (Slc14a2). Am J Physiol Renal Physiol 282(4):F630–F638

    CAS  PubMed  Google Scholar 

  25. Fenton RA, Hewitt JE, Howorth A, Cottingham CA, Smith CP (1999) The murine urea transporter genes Slc14a1 and Slc14a2 occur in tandem on chromosome 18. Cytogenet Cell Genet 87(1–2):95–96

    CAS  PubMed  Google Scholar 

  26. Fenton RA, Howorth A, Cooper GJ, Meccariello R, Morris ID, Smith CP (2000) Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis. Am J Physiol Cell Physiol 279(5):C1425–C1431

    CAS  PubMed  Google Scholar 

  27. Fenton RA, Shodeinde A, Knepper MA (2006) UT-A urea transporter promoter, UT-Aalpha, targets principal cells of the renal inner medullary collecting duct. Am J Physiol Renal Physiol 290(1):F188–F195

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Fenton RA, Stewart GS, Carpenter B, Howorth A, Potter EA, Cooper GJ, Smith CP (2002) Characterization of the mouse urea transporters UT-A1 and UT-A2. Am J Physiol Renal Physiol 283(4):F817–F825

    CAS  PubMed  Google Scholar 

  29. Fines GA, Ballantyne JS, Wright PA (2001) Active urea transport and an unusual basolateral membrane composition in the gills of a marine elasmobranch. Am J Physiol Regul Integr Comp Physiol 280(1):R16–R24

    CAS  PubMed  Google Scholar 

  30. Fröhlich O, Klein JD, Smith PM, Sands JM, Gunn RB (2004) Urea transport in MDCK cells that are stably transfected with UT-A1. Am J Physiol Cell Physiol 286(6):C1264–C1270

    PubMed  Google Scholar 

  31. Fröhlich O, Klein JD, Smith PM, Sands JM, Gunn RB (2006) Regulation of UT-A1-mediated transepithelial urea flux in MDCK cells. Am J Physiol Cell Physiol 291:C600–C606

    PubMed  Google Scholar 

  32. Fröhlich O, Macey RI, Edwards-Moulds J, Gargus JJ, Gunn RB (1991) Urea transport deficiency in Jk(a-b-) erythrocytes. Am J Physiol Cell Physiol 260:C778–C783

    Google Scholar 

  33. Hall GD, Smith B, Weeks RJ, Selby PJ, Southgate J, Chester JD (2006) Novel Urothelium specific gene expression identified by differential display reverse transcriptase-polymerase chain reaction. J Urol 175(1):337–342

    CAS  PubMed  Google Scholar 

  34. Hill WG, Southern NM, MacIver B, Potter E, Apodaca G, Smith CP, Zeidel ML (2005) Isolation and characterization of the Xenopus oocyte plasma membrane: a new method for studying activity of water and solute transporters. Am J Physiol Renal Physiol 289(1):F217–F224

    CAS  PubMed  Google Scholar 

  35. Hong X, Xing H, Yu Y, Wen Y, Zhang Y, Zhang S, Tang G, Xu X (2007) Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS. Methods Find Exp Clin Pharmacol 29(1):3–10

    CAS  PubMed  Google Scholar 

  36. Hu MC, Bankir L, Michelet S, Rousselet G, Trinh-Trang-Tan M-M (2000) Massive reduction of urea transporters in remnant kidney and brain of uremic rats. Kidney Int 58(3):1202–1210

    CAS  PubMed  Google Scholar 

  37. Hung CC, Nawata CM, Wood CM, Wright PA (2008) Rhesus glycoprotein and urea transporter genes are expressed in early stages of development of rainbow trout (Oncorhynchus mykiss). J Exp ZoolPart A EcolGenetPhysiol 309 (5):262–268. doi:10.1002/jez.456

  38. Hung CYC, Galvez F, Ip YK, Wood CM (2009) Increased gene expression of a facilitated diffusion urea transporter in the skin of the African lungfish (Protopterus annectens) during massively elevated post-terrestrialization urea excretion. J Exp Biol 212(8):1202–1211

    CAS  PubMed  Google Scholar 

  39. Hyodo S, Katoh F, Kaneko T, Takei Y (2004) A facilitative urea transporter is localized in the renal collecting tubule of the dogfish Triakis scyllia. J Exp Biol 207:347–356

    CAS  PubMed  Google Scholar 

  40. Inoue H, Jackson SD, Vikulina T, Klein JD, Tomita K, Bagnasco SM (2004) Identification and characterization of a Kidd antigen/UT-B urea transporter expressed in human colon. Am J Physiol Cell Physiol 287(1):C30–C35

    CAS  PubMed  Google Scholar 

  41. Inoue H, Kozlowski SD, Klein JD, Bailey JL, Sands JM, Bagnasco SM (2005) Regulated expression of the renal and intestinal UT-B urea transporter in response to varying urea load. Am J Physiol Renal Physiol 289(2):F451–F458

    CAS  PubMed  Google Scholar 

  42. Irshaid NM, Eicher NI, Hustinx H, Poole J, Olsson ML (2002) Novel alleles at the JK blood group locus explain the absence of the erythrocyte urea transporter in European families. Br J Haematol 116(2):445–453

    CAS  PubMed  Google Scholar 

  43. Irshaid NM, Henry SM, Olsson ML (2000) Genomic characterization of the kidd blood group gene: different molecular basis of the Jk(a-b-) phenotype in Polynesians and Finns. Transfusion 40(1):69–74

    CAS  PubMed  Google Scholar 

  44. Jung J-Y, Madsen KM, Han K-H, Yang C-W, Knepper MA, Sands JM, Kim J (2003) Expression of urea transporters in potassium-depleted mouse kidney. Am J Physiol Renal Physiol 285(6):F1210–F1224

    CAS  PubMed  Google Scholar 

  45. Kakumura K, Watanabe S, Bell JD, Donald JA, Toop T, Kaneko T, Hyodo S (2009) Multiple urea transporter proteins in the kidney of holocephalan elephant fish (Callorhinchus milii). Comp Biochem Physiol B Biochem Mol Biol 154 (2):239–247

    Google Scholar 

  46. Karakashian A, Timmer RT, Klein JD, Gunn RB, Sands JM, Bagnasco SM (1999) Cloning and characterization of two new mRNA isoforms of the rat renal urea transporter: UT-A3 and UT-A4. J Am Soc Nephrol 10(2):230–237

    CAS  PubMed  Google Scholar 

  47. Kim D-U, Klein JD, Racine S, Murrell BP, Sands JM (2005) Urea may regulate urea transporter protein abundance during osmotic diuresis. Am J Physiol Renal Physiol 288(1):F188–F197

    CAS  PubMed  Google Scholar 

  48. Kim Y-H, Kim D-U, Han K-H, Jung J-Y, Sands JM, Knepper MA, Madsen KM, Kim J (2002) Expression of urea transporters in the developing rat kidney. Am J Physiol Renal Physiol 282(3):F530–F540

    CAS  PubMed  Google Scholar 

  49. Kiran D, Mutsvangwa T (2010) Effects of partial ruminal defaunation on urea-nitrogen recycling, nitrogen metabolism, and microbial nitrogen supply in growing lambs fed low or high dietary crude protein concentrations. J Anim Sci 88(3):1034–1047

    CAS  PubMed  Google Scholar 

  50. Kishore BK, Terris J, Fernandez-Llama P, Knepper MA (1997) Ultramicro-determination of vasopressin-regulated renal urea transporter protein in microdissected renal tubules. Am J Physiol Renal Physiol 272(4):F531–F537

    CAS  Google Scholar 

  51. Klein JD, Blount MA, Sands JM (2011) Urea transport in the kidney. Compr Physiol Apr 1(2):699–729

    Google Scholar 

  52. Klein JD, Blount MA, Fröhlich O, Denson C, Tan X, Sim J, Martin CF, Sands JM (2010) Phosphorylation of UT-A1 on serine 486 correlates with membrane accumulation and urea transport activity in both rat IMCDs and cultured cells. Am J Physiol Renal Physiol 298(4):F935–F940

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Klein JD, Sands JM, Qian L, Wang X, Yang B (2004) Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. J Am Soc Nephrol 15(5):1161–1167

    CAS  PubMed  Google Scholar 

  54. Klein JD, Timmer RT, Rouillard P, Bailey JL, Sands JM (1999) UT-A urea transporter protein expressed in liver: upregulation by uremia. J Am Soc Nephrol 10(10):2076–2083

    CAS  PubMed  Google Scholar 

  55. Konno N, Hyodo S, Matsuda K, Uchiyama M (2006) Arginine vasotocin promotes urea permeability through urea transporter expressed in the toad urinary bladder cells. Gen Comp Endocrinol 152(2–3):281–285

    PubMed  Google Scholar 

  56. Konno N, Hyodo S, Matsuda K, Uchiyama M (2006) Effect of osmotic stress on expression of a putative facilitative urea transporter in the kidney and urinary bladder of the marine toad, Bufo marinus. J Exp Biol 209(7):1207–1216

    CAS  PubMed  Google Scholar 

  57. Kwun Y-S, Yeo SW, Ahn Y-H, Lim S-W, Jung J-Y, Kim W-Y, Sands JM, Kim J (2003) Immunohistochemical localization of urea transporters A and B in the rat cochlea. Hearing Res 183:84–96

    CAS  Google Scholar 

  58. Laurent P, Wood CM, Wang Y, Perry SF, Gilmour KM, Part P, Chevalier C, West M, Walsh PJ (2001) Intracellular vesicular trafficking in the gill epithelium of urea-excreting fish. Cell Tissue Res 303(2):197–210

    CAS  PubMed  Google Scholar 

  59. Levin MH, de la Fuente R, Verkman AS (2007) Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea transporter UT-B. FASEB J 21(2):551–563

    CAS  PubMed  Google Scholar 

  60. Li C, Klein JD, Wang W, Knepper MA, Nielsen S, Sands JM, Frokiaer J (2004) Altered expression of urea transporters in response to ureteral obstruction. Am J Physiol Renal Physiol 286(6):F1154–F1162

    CAS  PubMed  Google Scholar 

  61. Lim S-W, Han K-H, Jung J-Y, Kim W-Y, Yang C-W, Sands JM, Knepper MA, Madsen KM, Kim J (2006) Ultrastructural localization of UT-A and UT-B in rat kidneys with different hydration status. Am J Physiol Regul Integr Comp Physiol 290(2):R479–R492

    CAS  PubMed  Google Scholar 

  62. Lucien N, Bruneval P, Lasbennes F, Belair MF, Mandet C, Cartron JP, Bailly P, Trinh-Trang-Tan MM (2005) UT-B1 urea transporter is expressed along the urinary and gastrointestinal tracts of the mouse. Am J Physiol Regul Integr Comp Physiol 288(4):R1046–R1056

    CAS  PubMed  Google Scholar 

  63. Lucien N, Sidoux-Walter F, Olivès B, Moulds J, Le Pennec PY, Cartron JP, Bailly P (1998) Characterization of the gene encoding the human Kidd blood group urea transporter protein—evidence for splice site mutations in Jknull individuals. J Biol Chem 273(21):12973–12980

    CAS  PubMed  Google Scholar 

  64. Lucien N, Sidoux-Walter F, Roudier N, Ripoche P, Huet M, Trinh-Trang-Tan M-M, Cartron J-P, Bailly P (2002) Antigenic and functional properties of the human red blood cell urea transporter hUT-B1. J Biol Chem 277:34101–34108

    CAS  PubMed  Google Scholar 

  65. Ludden PA, Stohrer RM, Austin KJ, Atkinson RL, Belden EL, Harlow HJ (2009) Effect of protein supplementation on expression and distribution of urea transporter-B in lambs fed low-quality forage. J Anim Sci 87(4):1354–1365

    CAS  PubMed  Google Scholar 

  66. MacIver B, Smith CP, Hill WG, Zeidel ML (2008) Functional characterization of mouse urea transporters UT-A2 and UT-A3 expressed in purified Xenopus laevis oocyte plasma membranes. Am J Physiol Renal Physiol 294(4):F956–F964

    CAS  PubMed  Google Scholar 

  67. Mannuzzu LM, Moronne MM, Macey RI (1993) Estimate of the number of urea transport sites in erythrocyte ghosts using a hydrophobic mercurial. J Membr Biol 133:85–97

    CAS  PubMed  Google Scholar 

  68. Marini JC, Klein JD, Sands JM, Van Amburgh ME (2004) Effect of nitrogen intake on nitrogen recycling and urea transporter abundance in lambs. J Anim Sci 82:1157–1164

    CAS  PubMed  Google Scholar 

  69. Martial S, Olives B, Abrami L, Couriaud C, Bailly P, You G, Hediger MA, Cartron J-P, Ripoche P, Rousselet G (1996) Functional differentiation of the human red blood cell and kidney urea transporters. Am J Physiol Renal Physiol 271(6):F1264–F1268

    CAS  Google Scholar 

  70. McDonald MD, Smith CP, Walsh PJ (2006) The physiology and evolution of urea transport in fishes. J Membr Biol 212 (2):93–107

    Google Scholar 

  71. McDonald MD, Vulesevic B, Perry SF, Walsh PJ (2009) Urea transporter and glutamine synthetase regulation and localization in gulf toadfish gill. J Exp Biol 212(5):704–712

    CAS  PubMed  Google Scholar 

  72. McDonald MD, Walsh PJ, Wood CM (2002) Branchial and renal excretion of urea and urea analogues in the plainfin midshipman, Porichthys notatus. J Comp Physiol B Biochem System Environ Physiol 172(8):699–712

    CAS  Google Scholar 

  73. McDonald MD, Wood CM, Wang YX, Walsh PJ (2000) Differential branchial and renal handling of urea, acetamide and thiourea in the gulf toadfish Opsanus beta: evidence for two transporters. J Exp Biol 203(6):1027–1037

    CAS  PubMed  Google Scholar 

  74. Minocha R, Studley K, Saier MH Jr (2003) The urea transporter (UT) family: bioinformatic analyses leading to structural, functional, and evolutionary predictions. Receptor Channel 9:345–352

    CAS  Google Scholar 

  75. Mistry AC, Chen G, Kato A, Nag K, Sands JM, Hirose S (2005) A novel type of urea transporter, UT-C, highly expressed in proximal tubule of seawater eel kidney. Am J Physiol Renal Physiol 288(3):F455–F465

    CAS  PubMed  Google Scholar 

  76. Morgan RL, Ballantyne JS, Wright PA (2003) Regulation of a renal urea transporter with reduced salinity in a marine elasmobranch. Raja erinacea. J Exp Biol 206(18):3285–3292

    CAS  Google Scholar 

  77. Morgan RL, Wright PA, Ballantyne JS (2003) Urea transport in kidney brush-border membrane vesicles from an elasmobranch, Raja erinacea. J Exp Biol 206(18):3293–3302

    CAS  PubMed  Google Scholar 

  78. Nakayama Y, Naruse M, Karakashian A, Peng T, Sands JM, Bagnasco SM (2001) Cloning of the rat Slc14a2 gene and genomic organization of the UT-A urea transporter. Biochim Biophys Acta 1518:19–26

    CAS  PubMed  Google Scholar 

  79. Nakayama Y, Peng T, Sands JM, Bagnasco SM (2000) The TonE/TonEBP pathway mediates tonicity-responsive regulation of UT-A urea transporter expression. J Biol Chem 275(49):38275–38280

    CAS  PubMed  Google Scholar 

  80. Naruse M, Klein JD, Ashkar ZM, Jacobs JD, Sands JM (1997) Glucocorticoids downregulate the rat vasopressin-regulated urea transporter in rat terminal inner medullary collecting ducts. J Am Soc Nephrol 8(4):517–523

    CAS  PubMed  Google Scholar 

  81. Neau P, Degeilh F, Lamotte H, Rousseau B, Ripoche P (1993) Photoaffinity labeling of the human red-blood-cell urea- transporter polypeptide components–possible homology with the kidd blood group antigen. Eur J Biochem 218:447–455

    CAS  PubMed  Google Scholar 

  82. Nielsen S, Terris J, Smith CP, Hediger MA, Ecelbarger CA, Knepper MA (1996) Cellular and subcellular localization of the vasopressin-regulated urea transporter in rat kidney. Proc Natl Acad Sci USA 93:5495–5500

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Ogami A, Miyazaki H, Niisato N, Sugimoto T, Marunaka Y (2006) UT-B1 urea transporter plays a noble role as active water transporter in C6 glial cells. Biochem Biophys Res Commun 351(3):619–624

    CAS  PubMed  Google Scholar 

  84. Olivès B, Martial S, Mattei MG, Matassi G, Rousselet G, Ripoche P, Cartron JP, Bailly P (1996) Molecular characterization of a new urea transporter in the human kidney. FEBS Lett 386(2–3):156–160

    PubMed  Google Scholar 

  85. Olivès B, Mattei M-G, Huet M, Neau P, Martial S, Cartron J-P, Bailly P (1995) Kidd blood group and urea transport function of human erythrocytes are carried by the same protein. J Biol Chem 270:15607–15610

    PubMed  Google Scholar 

  86. Olives B, Merriman M, Bailly P, Bain S, Barnett A, Todd J, Cartron JP, Merriman T (1997) The molecular basis of the Kidd blood group polymorphism and its lack of association with type 1 diabetes susceptibility. Hum Mol Genet 6(7):1017–1020

    CAS  PubMed  Google Scholar 

  87. Olives B, Neau P, Bailly P, Hediger MA, Rousselet G, Cartron JP, Ripoche P (1994) Cloning and functional expression of a urea transporter from human bone marrow cells. J Biol Chem 269(50):31649–31652

    CAS  PubMed  Google Scholar 

  88. Pallone T, Zhang Z, Rhinehart K (2003) Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284:F253–F266

    CAS  PubMed  Google Scholar 

  89. Pannabecker TL, Dahlmann A, Brokl OH, Dantzler WH (2000) Mixed descending- and ascending-type thin limbs of Henle’s loop in mammalian renal inner medulla. Am J Physiol Renal Physiol 278(2):F202–F208

    CAS  PubMed  Google Scholar 

  90. Pannabecker TL, Dantzler WH, Layton HE, Layton AT (2008) Role of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla. Am J Physiol Renal Physiol 295(5):F1271–F1285

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Pannabecker TL, Henderson CS, Dantzler WH (2008) Quantitative analysis of functional reconstructions reveals lateral and axial zonation in the renal inner medulla. Am J Physiol Renal Physiol 294(6):F1306–F1314

    CAS  PubMed  Google Scholar 

  92. Peng T, Sands JM, Bagnasco SM (2002) Glucocorticoids inhibit transcription and expression of the rat UT-A urea transporter gene. Am J Physiol Renal Physiol 282(5):F853–F858

    CAS  PubMed  Google Scholar 

  93. Pilley CM, Wright PA (2000) The mechanisms of urea transport by early life stages of rainbow trout (Oncorhynchus mykiss). J Exp Biol 203(20):3199–3207

    CAS  PubMed  Google Scholar 

  94. Potter EA, Stewart G, Smith CP (2006) Urea flux across MDCK-mUT-A2 monolayers is acutely sensitive to AVP, cAMP, and [Ca2+]i. Am J Physiol Renal Physiol 291(1):F122–F128

    CAS  PubMed  Google Scholar 

  95. Prichett WP, Patton AJ, Field JA, Brun KA, Emery JG, Tan KB, Rieman DJ, McClung HA, Nadeau DP, Mooney JL, Suva LJ, Gowen M, Nuttall ME (2000) Identification and cloning of a human urea transporter HUT11, which is downregulated during adipogenesis of explant cultures of human bone. J Cell Biochem 76(4):639–650

    CAS  PubMed  Google Scholar 

  96. Promeneur D, Rousselet G, Bankir L, Bailly P, Cartron JP, Ripoche P, Trinh-Trang-Tan MM (1996) Evidence for distinct vascular and tubular urea transporters in the rat kidney. J Am Soc Nephrol 7(6):852–860

    CAS  PubMed  Google Scholar 

  97. Ranade K, Wu KD, Hwu CM, Ting CT, Pei D, Pesich R, Hebert J, Chen YDI, Pratt R, Olshen R, Masaki K, Risch N, Cox DR, Botstein D (2001) Genetic variation in the human urea transporter-2 is associated with variation in blood pressure. Hum Mol Genet 10(19):2157–2164

    CAS  PubMed  Google Scholar 

  98. Ritzhaupt A, Wood IS, Jackson AA, Moran BJ, Shirazi-Beechey SP (1998) Isolation of a RT-PCR fragment from human colon and sheep rumen RNA with nucleotide sequence similarity to human and rat urea transporter isoforms. Biochem Soc Trans 26:S122

    CAS  PubMed  Google Scholar 

  99. Rodela TM, Gilmour KM, Walsh PJ, McDonald MD (2009) Cortisol-sensitive urea transport across the gill basolateral membrane of the gulf toadfish (Opsanus beta). Am J Physiol Regul Integr Comp Physiol 297(2):R313–R322

    CAS  PubMed  Google Scholar 

  100. Rousselet G, Ripoche P, Bailly P (1996) Tandem sequence repeats in urea transporters: Identification, of an urea transporter signature sequence. Am J Physiol Renal Physiol 270(3):F554–F555

    CAS  Google Scholar 

  101. Sands JM (1999) Regulation of renal urea transporters. J Am Soc Nephrol 10(3):635–646

    CAS  PubMed  Google Scholar 

  102. Sands JM (1999) Urea transport: It’s not just “freely diffusible” anymore. News Physiol Sci 14(1):46–47

    PubMed  Google Scholar 

  103. Sands JM, Gargus JJ, Fröhlich O, Gunn RB, Kokko JP (1992) Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport. J Am Soc Nephrol 2:1689–1696

    CAS  PubMed  Google Scholar 

  104. Sands JM, Timmer RT, Gunn RB (1997) Urea transporters in kidney and erythrocytes. Am J Physiol Renal Physiol 273(3):F321–F339

    CAS  Google Scholar 

  105. Schmidt C, Hocherl K, Bucher M (2007) Cytokine-mediated regulation of urea transporters during experimental endotoxemia. Am J Physiol Renal Physiol 292(5):F1479–F1489

    CAS  PubMed  Google Scholar 

  106. Shayakul C, Knepper MA, Smith CP, DiGiovanni SR, Hediger MA (1997) Segmental localization of urea transporter mRNAs in rat kidney. Am J Physiol Renal Physiol 272(5):F654–F660

    CAS  Google Scholar 

  107. Shayakul C, Steel A, Hediger MA (1996) Molecular cloning and characterization of the vasopressin-regulated urea transporter of rat kidney collecting ducts. J Clin Invest 98(11):2580–2587

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Shayakul C, Tsukaguchi H, Berger UV, Hediger MA (2001) Molecular characterization of a novel urea transporter from kidney inner medullary collecting ducts. Am J Physiol Renal Physiol 280(3):F487–F494

    CAS  PubMed  Google Scholar 

  109. Sidoux-Walter F, Lucien N, Nissinen R, Sistonen P, Henry S, Moulds J, Cartron J-P, Bailly P (2000) Molecular heterogeneity of the Jknull phenotype: expression analysis of the Jk(S291P) mutation found in Finns. Blood 96(4):1566–1573

    CAS  PubMed  Google Scholar 

  110. Sidoux-Walter F, Lucien N, Olivès B, Gobin R, Rousselet G, Kamsteeg EJ, Ripoche P, Deen PMT, Cartron JP, Bailly P (1999) At physiological expression levels the Kidd blood group/urea transporter protein is not a water channel. J Biol Chem 274(42):30228–30235

    CAS  PubMed  Google Scholar 

  111. Simmons NL, Chaudhry AS, Graham C, Scriven ES, Thistlethwaite A, Smith CP, Stewart GS (2009) Dietary regulation of ruminal bUT-B urea transporter expression and localization. J Anim Sci 87(10):3288–3299

    CAS  PubMed  Google Scholar 

  112. Smith CP, Fenton RA (2006) Genomic organization of the mammalian SLC14a2 urea transporter genes. J Membr Biol 212(2):109–117

    CAS  PubMed  Google Scholar 

  113. Smith CP, Lee W-S, Martial S, Knepper MA, You G, Sands JM, Hediger MA (1995) Cloning and regulation of expression of the rat kidney urea transporter (rUT2). J Clin Invest 96(3):1556–1563

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Smith CP, Potter EA, Fenton RA, Stewart GS (2004) Characterization of a human colonic cDNA encoding a structurally novel urea transporter, UT-A6. Am J Physiol Cell Physiol 287(4):C1087–C1093

    CAS  PubMed  Google Scholar 

  115. Spector DA, Yang Q, Liu J, Wade JB (2004) Expression, localization, and regulation of urea transporter B in rat urothelia. Am J Physiol Renal Physiol 287(1):F102–F108

    CAS  PubMed  Google Scholar 

  116. Spector DA, Yang Q, Wade JB (2007) High urea and creatinine concentrations and urea transporter B in mammalian urinary tract tissues. Am J Physiol Renal Physiol 292(1):F467–F474

    CAS  PubMed  Google Scholar 

  117. Stewart G (2011) The emerging physiological roles of the SLC14A family of urea transporters. Br J Pharmacol 164:1780–1792

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Stewart GS, Fenton RA, Wang W, Kwon TH, White SJ, Collins VM, Cooper G, Nielsen S, Smith CP (2004) The basolateral expression of mUT-A3 in the mouse kidney. Am J Physiol Renal Physiol 286(5):F979–F987

    CAS  PubMed  Google Scholar 

  119. Stewart GS, Graham C, Cattell S, Smith TPL, Simmons NL, Smith CP (2005) UT-B is expressed in bovine rumen: potential role in ruminal urea transport. Am J Physiol Regul Integr Comp Physiol 289(2):R605–R612

    CAS  PubMed  Google Scholar 

  120. Stewart GS, King SL, Potter EA, Smith CP (2007) Acute regulation of the urea transporter mUT-A3 expressed in a MDCK cell line. Am J Physiol Renal Physiol 292(4):F1157–F1163

    CAS  PubMed  Google Scholar 

  121. Terris J, Ecelbarger CA, Sands JM, Knepper MA (1998) Long-term regulation of collecting duct urea transporter proteins in rat. J Am Soc Nephrol 9(5):729–736

    CAS  PubMed  Google Scholar 

  122. Terris JM, Knepper MA, Wade JB (2001) UT-A3: localization and characterization of an additional urea transporter isoform in the IMCD. Am J Physiol Renal Physiol 280(2):F325–F332

    CAS  PubMed  Google Scholar 

  123. Tickle P, Thistlethwaite A, Smith CP, Stewart GS (2009) Novel bUT-B2 urea transporter isoform is constitutively activated. Am J Physiol Regul Integr Comp Physiol 297(2):R323–R329

    CAS  PubMed  Google Scholar 

  124. Timmer RT, Klein JD, Bagnasco SM, Doran JJ, Verlander JW, Gunn RB, Sands JM (2001) Localization of the urea transporter UT-B protein in human and rat erythrocytes and tissues. Am J Physiol Cell Physiol 281(4):C1318–C1325

    CAS  PubMed  Google Scholar 

  125. Trinh-Trang-Tan M-M, Cartron JP, Bankir L (2005) Molecular basis for the dialysis disequilibrium syndrome: altered aquaporin and urea transporter expression in the brain. Nephrol Dial Transplant 20(9):1984–1988

    CAS  PubMed  Google Scholar 

  126. Trinh-Trang-Tan M-M, Lasbennes F, Gane P, Roudier N, Ripoche P, Cartron J-P, Bailly P (2002) UT-B1 proteins in rat: tissue distribution and regulation by antidiuretic hormone in kidney. Am J Physiol Renal Physiol 283(5):F912–F922

    PubMed  Google Scholar 

  127. Tsukaguchi H, Shayakul C, Berger UV, Tokui T, Brown D, Hediger MA (1997) Cloning and characterization of the urea transporter UT3. Localization in rat kidney and testis. J Clin Invest 99(7):1506–1515

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Uchiyama M, Kikuchi R, Konno N, Wakasugi T, Matsuda K (2009) Localization and regulation of a facilitative urea transporter in the kidney of the red-eared slider turtle (Trachemys scripta elegans). J Exp Biol 212(2):249–256

    CAS  PubMed  Google Scholar 

  129. Uchiyama M, Konno N (2006) Hormonal regulation of ion and water transport in anuran amphibians. Gen Comp Endocrinol 147(1):54–61

    CAS  PubMed  Google Scholar 

  130. Wade JB, Lee AJ, Liu J, Ecelbarger CA, Mitchell C, Bradford AD, Terris J, Kim G-H, Knepper MA (2000) UT-A2: a 55 kDa urea transporter protein in thin descending limb of Henle’s loop whose abundance is regulated by vasopressin. Am J Physiol Renal Physiol 278(1):F52–F62

    CAS  PubMed  Google Scholar 

  131. Wagner L, Klein JD, Sands JM, Baylis C (2002) Urea transporters are widely distributed in endothelial cells and mediate inhibition of L-arginine transport. Am J Physiol Renal Physiol 283(3):F578–F582

    CAS  PubMed Central  PubMed  Google Scholar 

  132. Walsh PJ, Grosell M, Goss GG, Bergman HL, Bergman AN, Wilson P, Laurent P, Alper SL, Smith CP, Kamunde C, Wood CM (2001) Physiological and molecular characterization of urea transport by the gills of the Lake Magadi tilapia (Alcolapia grahami). J Exp Biol 204(3):509–520

    CAS  PubMed  Google Scholar 

  133. Walsh PJ, Wood CM, Perry SF, Thomas S (1994) Urea transport by hepatocytes and red blood cells of selected elasmobrach and teleost fishes. J Exp Med 193:321–335

    CAS  Google Scholar 

  134. Wester ES, Johnson ST, Copeland T, Malde R, Lee E, Storry JR, Olsson ML (2008) Erythroid urea transporter deficiency due to novel JKnull alleles. Transfusion 48 (2):365–372

    Google Scholar 

  135. Wilkie MP (2002) Ammonia excretion and urea handling by fish gills: present understanding and future research challenges. J Exp Zool 293(3):284–301

    CAS  PubMed  Google Scholar 

  136. C-á Wood, P-á Walsh, S-á Chew, Y-á Ip (2005) Greatly elevated urea excretion after air exposure appears to be carrier mediated in the slender lungfish (Protopterus dolloi). Physiol Biochem Zool 78(6):893–907

    Google Scholar 

  137. Wood CM, McDonald MD, Sundin L, Laurent P, Walsh PJ (2003) Pulsatile urea excretion in the gulf toadfish: mechanisms and controls. Comp Biochem Physiol B: Biochem Mol Biol 136(4):667–684

    Google Scholar 

  138. Wood CM, Warne JM, Wang YX, McDonald MD, Balment RJ, Laurent P, Walsh PJ (2001) Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion in the gulf toadfish (Opsanus beta)? Comp Biochem Physiol A: Mol Integr Physiol 129(4):859–872

    CAS  Google Scholar 

  139. Wright PA, Land MD (1998) Urea production and transport in teleost fishes. Comp Biochem Physiol A Comp Physiol 119A(1):47–54

    CAS  Google Scholar 

  140. Xu Y, Olives B, Bailly P, Fischer E, Ripoche P, Ronco P, Cartron J-P, Rondeau E (1997) Endothelial cells of the kidney vasa recta express the urea transporter HUT11. Kidney Int 51(1):138–146

    CAS  PubMed  Google Scholar 

  141. Yamaguchi Y, Takaki S, Hyodo S (2009) Subcellular distribution of urea transporter in the collecting tubule of shark kidney is dependent on environmental salinity. J Exp Zool A Ecol Genet Physiol 311(9):705–718

    PubMed  Google Scholar 

  142. Yang B, Bankir L, Gillespie A, Epstein CJ, Verkman AS (2002) Urea-selective concentrating defect in transgenic mice lacking urea transporter UT-B. J Biol Chem 277:10633–10637

    CAS  PubMed  Google Scholar 

  143. Yang BX, Verkman AS (1998) Urea transporter UT3 functions as an efficient water channel—direct evidence for a common water/urea pathway. J Biol Chem 273(16):9369–9372

    CAS  PubMed  Google Scholar 

  144. You G, Smith CP, Kanai Y, Lee W-S, Stelzner M, Hediger MA (1993) Cloning and characterization of the vasopressin-regulated urea transporter. Nature 365:844–s847

    CAS  PubMed  Google Scholar 

  145. Yuan J, Pannabecker TL (2010) Architecture of inner medullary descending and ascending vasa recta: pathways for countercurrent exchange. Am J Physiol Renal Physiol 299(1):F265–F272

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Zhai XY, Fenton RA, Andreasen A, Thomsen JS, Christensen AE (2007) Aquaporin-1 is not expressed in descending thin limbs of short-loop nephrons. J Am Soc Nephrol 18:2937–2944

    PubMed  Google Scholar 

  147. Zhao D, Sonawane ND, Levin MH, Yang B (2007) Comparative transport efficiencies of urea analogues through urea transporter UT-B. Biochim Biophys Acta Biomembranes 1768(7):1815–1821

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH Grants R01-DK89828 and R21-DK91147 to JMS and K01-DK82733 and R01-DK91501 to MAB.

Author information

Authors and Affiliations

  1. Renal Division, Department of Medicine and Department of Physiology, Emory University School of Medicine, WMB Room 338, 1639 Pierce Drive, NE, Atlanta, GA, 30322, USA

    Jeff M. Sands & Mitsi A. Blount

Authors
  1. Jeff M. Sands
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsi A. Blount
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeff M. Sands .

Editor information

Editors and Affiliations

  1. School of Basic Medical Sciences, Department of Pharmacology, Peking University, Beijing, China

    Baoxue Yang

  2. Renal Division, Department of Medicine and Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, USA

    Jeff M. Sands

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Sands, J.M., Blount, M.A. (2014). Genes and Proteins of Urea Transporters. In: Yang, B., Sands, J. (eds) Urea Transporters. Subcellular Biochemistry, vol 73. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9343-8_4

Download citation

Publish with us

Policies and ethics

Search

Navigation