Advertisement

The Journal of Membrane Biology

, Volume 239, Issue 3, pp 123–130 | Cite as

UT-B1 Mediates Transepithelial Urea Flux in the Rat Gastrointestinal Tract

  • Danielle Collins
  • Caragh Walpole
  • Elizabeth Ryan
  • Desmond Winter
  • Alan Baird
  • Gavin Stewart
Article

Abstract

The process of urea nitrogen salvaging plays a vital role in the symbiotic relationship between mammals and their intestinal bacteria. The first step in this process requires the movement of urea from the mammalian bloodstream into the gastrointestinal tract lumen via specialized proteins known as facilitative urea transporters. In this study, we examined both transepithelial urea fluxes and urea transporter protein abundance along the length of the rat gastrointestinal tract. Urea flux experiments that used rat gastrointestinal tissues showed significantly higher transepithelial urea transport was present in caecum and proximal colon (P < 0.01, n = 8, analysis of variance [ANOVA]). This large urea flux was significantly inhibited by 1,3,dimethylurea (P < 0.001, n = 8, ANOVA) and thiourea (P < 0.05, n = 6, unpaired t-test), both known blockers of facilitative urea transporters. Immunoblotting analysis failed to detect any UT-A protein within rat gastrointestinal tissue protein samples. In contrast, a 30-kDa UT-B1 protein was strongly detected in both caecum and proximal colon samples at significantly higher levels compared to the rest of the gastrointestinal tract (P < 0.01, n = 4, ANOVA). We therefore concluded that UT-B1 mediates the transepithelial movement of urea that occurs in specific distal regions of the rat gastrointestinal tract.

Keywords

UT-A UT-B Transepithelial urea transport Dimethylurea Intestine Colon 

Notes

Acknowledgment

This work was funded by the Irish Research Council for Science, Engineering and Technology (IRCSET) postgraduate scholarship scheme.

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:G190–G202CrossRefPubMedGoogle Scholar
  2. Collins D, Winter DC, Hogan AM, Schirmer L, Baird AW, Stewart GS (2010) Differential protein abundance and function of UT-B urea transporters in human colon. Am J Physiol Gastrointest Liver Physiol 298:G345–G351CrossRefPubMedGoogle Scholar
  3. Fihn BM, Jodal M (2001) Permeability of the proximal and distal rat colon crypt and surface epithelium to hydrophilic molecules. Pflugers Arch 441:656–662CrossRefPubMedGoogle Scholar
  4. Hopkins AM, McDonnell C, Breslin NP, O’Morain CA, Baird AW (2002) Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue. J Pharm Pharmacol 54:341–347CrossRefPubMedGoogle Scholar
  5. 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:C30–C35CrossRefPubMedGoogle Scholar
  6. Inoue H, Kozlowski SD, Klein JD, Bailey JL, Sands JM, Bagnasco SM (2005) Regulated expression of renal and intestinal UT-B urea transporter in response to varying urea load. Am J Physiol Renal Physiol 289:F451–F458CrossRefPubMedGoogle Scholar
  7. Iwanga T, Takebe K, Kato I, Karaki S, Kuwahara A (2006) Cellular expression of monocarboxylate transporters in the digestive tract of mouse, rats and humans, with special reference to slc5a8. Biomed Res 27:243–254CrossRefGoogle Scholar
  8. Kirat D, Kondo K, Shimada R, Kato S (2009) Dietary pectin up-regulates monocarboxylate transporter 1 in the rat gastrointestinal tract. Exp Physiol 94:422–433CrossRefPubMedGoogle Scholar
  9. 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:R1046–R1056PubMedGoogle Scholar
  10. 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 87:1354–1365CrossRefPubMedGoogle Scholar
  11. 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:F956–F964CrossRefPubMedGoogle Scholar
  12. Nugent SG, Kumar D, Rampton DS, Evans DF (2001) Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 48:571–577CrossRefPubMedGoogle Scholar
  13. Simmons NL, Chaudhry AS, Graham C, Scriven ES, Thistlethwaite A, Smith CP, Stewart GS (2009) Dietary regulation of ruminal bovine UT-B urea transporter expression and localization. J Anim Sci 87:3288–3299CrossRefPubMedGoogle Scholar
  14. Smith CP (2008) Mammalian urea transporters. Exp Physiol 94:180–185CrossRefPubMedGoogle Scholar
  15. Smith CP, Rousselet G (2001) Urea transporters. J Membr Biol 183:1–14CrossRefPubMedGoogle Scholar
  16. Stewart GS, Smith CP (2005) Urea nitrogen salvage mechanisms and their relevance to ruminants, non-ruminants and man. Nutr Res Rev 18:49–62CrossRefPubMedGoogle Scholar
  17. Stewart GS, Fenton RA, Wang W, Kwon TH, White SJ, Collins VM, Cooper GJ, Nielsen S, Smith CP (2004) The basolateral expression of mUT-A3 in the mouse kidney. Am J Physiol Renal Physiol 286:F979–F987CrossRefPubMedGoogle Scholar
  18. Stewart GS, Graham C, Cattell S, Smith TPL, Simmons NL, Smith CP (2005) UT-B is expressed in bovine rumen: a potential role in ruminal urea transport. Am J Physiol Regul Integr Comp Physiol 289:R605–R612PubMedGoogle Scholar
  19. Stewart GS, Thistlethwaite A, Lees H, Cooper GJ, Smith CP (2009) Vasopressin regulation of the renal UT-A3 urea transporter. Am J Physiol Renal Physiol 296:F642–F648CrossRefPubMedGoogle Scholar
  20. Talbot C, Lytle C (2010) Segregation of Na/H exchanger-3 and Cl/HCO3 exchanger SLC26A3 (DRA) in rodent cecum and colon. Am J Physiol Gastrointest Liver Physiol 299:G358–G367CrossRefPubMedGoogle Scholar
  21. 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:R323–R329PubMedGoogle Scholar
  22. 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:C1318–C1325PubMedGoogle Scholar
  23. Trinh-Trang-Tan MM, Lasbennes F, Gane P, Roudier N, Ripoche R, Cartron JP, Bailly P (2002) UT-B1 proteins in rat: tissue distribution and regulation by antidiuretic hormone in kidney. Am J Physiol Renal Physiol 283:F912–F922PubMedGoogle Scholar
  24. Yang B, Bankir L (2005) Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol 288:F881–F896CrossRefPubMedGoogle Scholar
  25. Yang B, Verkman AS (2002) Analysis of double knockout mice lacking aquaporin 1 and urea transporter UT-B. Evidence for UT-B facilitated water transport in erythrocytes. J Biol Chem 277:36782–36786CrossRefPubMedGoogle Scholar
  26. Zhao D, Sonawane ND, Levin MH, Yang B (2007) Comparative transport efficiencies of urea analogues through urea transporter UT-B. Biochim Biophys Acta 1768:1815–1821CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Danielle Collins
    • 1
    • 2
  • Caragh Walpole
    • 3
  • Elizabeth Ryan
    • 1
    • 2
  • Desmond Winter
    • 1
  • Alan Baird
    • 2
  • Gavin Stewart
    • 3
  1. 1.Institute for Clinical Outcomes Research and EducationSt. Vincent’s University HospitalDublinIreland
  2. 2.College of Life SciencesConway Institute of Biomedical and Biomolecular ScienceDublinIreland
  3. 3.School of Biology and Environmental ScienceUniversity College Dublin BelfieldDublinIreland

Personalised recommendations