Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Sep;80(3):684–690. doi: 10.1172/JCI113122

Ursodeoxycholate stimulates Na+-H+ exchange in rat liver basolateral plasma membrane vesicles.

R H Moseley, N Ballatori, D J Smith, J L Boyer
PMCID: PMC442291  PMID: 3040805

Abstract

Na+:H+ and Cl-:HCO3- exchange are localized, respectively, to basolateral (blLPM) and canalicular (cLPM) rat liver plasma membranes. To determine whether these exchangers play a role in bile formation, we examined the effect of a choleretic agent, ursodeoxycholate (UDCA), on these exchange mechanisms. 22Na (1 mM) and 36Cl (5 mM) uptake was determined using outwardly directed H+ and HCO3- gradients, respectively. Preincubation of blLPM vesicles with UDCA (0-500 microM) resulted in a concentration-dependent increase in initial rates of amiloride-sensitive pH-driven Na+ uptake, with a maximal effect at 200 microM. UDCA (200 microM) increased Vmax from 23 +/- 2 (control) to 37 +/- 7 nmol/min per mg protein; apparent Km for Na+ was unchanged. Preincubation with tauroursodeoxycholate (200 microM), taurocholate (10-200 microM) or cholate, chenodeoxycholate, or deoxycholate (200 microM) had no effect on pH-driven Na+ uptake. UDCA (200 microM) had no effect on either membrane lipid fluidity, assessed by steady-state fluorescence polarization using the probes 1,6-diphenyl-1,3,5-hexatriene, 12-(9-anthroyloxy) stearic acid, and 2-(9-anthroyloxy) stearic acid (2-AS), or Na+,K+-ATPase activity in blLPM vesicles. In cLPM vesicles, UDCA (0-500 microM) had no stimulatory effect on initial rates of HCO3(-)-driven Cl- uptake. Enhanced basolateral Na+:H+ exchange activity, leading to intracellular HCO3- concentrations above equilibrium, may account for the bicarbonate-rich choleresis after UDCA infusion.

Full text

PDF
684

Images in this article

686Image
on p.686
686Image
on p.686
687Image
on p.687

Selected References

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

  1. Anwer M. S., Hegner D. Role of inorganic electrolytes in bile acid-independent canalicular bile formation. Am J Physiol. 1983 Feb;244(2):G116–G124. doi: 10.1152/ajpgi.1983.244.2.G116. [DOI] [PubMed] [Google Scholar]
  2. Aronson P. S., Nee J., Suhm M. A. Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature. 1982 Sep 9;299(5879):161–163. doi: 10.1038/299161a0. [DOI] [PubMed] [Google Scholar]
  3. Brasitus T. A., Dudeja P. K., Worman H. J., Foster E. S. The lipid fluidity of rat colonic brush-border membrane vesicles modulates Na+-H+ exchange and osmotic water permeability. Biochim Biophys Acta. 1986 Feb 13;855(1):16–24. doi: 10.1016/0005-2736(86)90183-5. [DOI] [PubMed] [Google Scholar]
  4. Dudeja P. K., Foster E. S., Brasitus T. A. Regulation of Na+-H+ exchange by transmethylation reactions in rat colonic brush-border membranes. Biochim Biophys Acta. 1986 Jul 10;859(1):61–68. doi: 10.1016/0005-2736(86)90318-4. [DOI] [PubMed] [Google Scholar]
  5. Dumont M., Erlinger S., Uchman S. Hypercholeresis induced by ursodeoxycholic acid and 7-ketolithocholic acid in the rat: possible role of bicarbonate transport. Gastroenterology. 1980 Jul;79(1):82–89. [PubMed] [Google Scholar]
  6. Erlinger S., Dhumeaux D., Berthelot P., Dumont M. Effect of inhibitors of sodium transport on bile formation in the rabbit. Am J Physiol. 1970 Aug;219(2):416–422. doi: 10.1152/ajplegacy.1970.219.2.416. [DOI] [PubMed] [Google Scholar]
  7. Fuchs R., Thalhammer T., Peterlik M., Graf J. Electrical and molecular coupling between sodium and proton fluxes in basolateral membrane vesicles of rat liver. Pflugers Arch. 1986 Apr;406(4):430–432. doi: 10.1007/BF00590949. [DOI] [PubMed] [Google Scholar]
  8. Garcia-Marin J. J., Corbic M., Dumont M., de Couët G., Erlinger S. Role of H+ transport in ursodeoxycholate-induced biliary HCO-3 secretion in the rat. Am J Physiol. 1985 Sep;249(3 Pt 1):G335–G341. doi: 10.1152/ajpgi.1985.249.3.G335. [DOI] [PubMed] [Google Scholar]
  9. Garcia-Marin J. J., Dumont M., Corbic M., de Couet G., Erlinger S. Effect of acid-base balance and acetazolamide on ursodeoxycholate-induced biliary bicarbonate secretion. Am J Physiol. 1985 Jan;248(1 Pt 1):G20–G27. doi: 10.1152/ajpgi.1985.248.1.G20. [DOI] [PubMed] [Google Scholar]
  10. Graf J., Gautam A., Boyer J. L. Isolated rat hepatocyte couplets: a primary secretory unit for electrophysiologic studies of bile secretory function. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6516–6520. doi: 10.1073/pnas.81.20.6516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hardison W. G., Wood C. A. Importance of bicarbonate in bile salt independent fraction of bile flow. Am J Physiol. 1978 Aug;235(2):E158–E164. doi: 10.1152/ajpendo.1978.235.2.E158. [DOI] [PubMed] [Google Scholar]
  12. Henderson R. M., Graf J., Boyer J. L. Na-H exchange regulates intracellular pH in isolated rat hepatocyte couplets. Am J Physiol. 1987 Jan;252(1 Pt 1):G109–G113. doi: 10.1152/ajpgi.1987.252.1.G109. [DOI] [PubMed] [Google Scholar]
  13. Kinsella J. L., Aronson P. S. Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles. Am J Physiol. 1981 Oct;241(4):F374–F379. doi: 10.1152/ajprenal.1981.241.4.F374. [DOI] [PubMed] [Google Scholar]
  14. Kinsella J., Cujdik T., Sacktor B. Na+-H+ exchange activity in renal brush border membrane vesicles in response to metabolic acidosis: The role of glucocorticoids. Proc Natl Acad Sci U S A. 1984 Jan;81(2):630–634. doi: 10.1073/pnas.81.2.630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kinsella J., Sacktor B. Thyroid hormones increase Na+-H+ exchange activity in renal brush border membranes. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3606–3610. doi: 10.1073/pnas.82.11.3606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kitani K., Kanai S. Biliary transport maximum of tauroursodeoxycholate is twice as high as that of taurocholate in the rat. Life Sci. 1981 Jul 20;29(3):269–275. doi: 10.1016/0024-3205(81)90243-5. [DOI] [PubMed] [Google Scholar]
  17. Kitani K., Kanai S. Effect of ursodeoxycholate on the bile flow in the rat. Life Sci. 1982 Nov 1;31(18):1973–1985. doi: 10.1016/0024-3205(82)90036-4. [DOI] [PubMed] [Google Scholar]
  18. Kitani K., Kanai S. Effect of ursodeoxycholate on the bile flow in the rat. Life Sci. 1982 Nov 1;31(18):1973–1985. doi: 10.1016/0024-3205(82)90036-4. [DOI] [PubMed] [Google Scholar]
  19. Lake J. R., Van Dyke R. W., Scharschmidt B. F. Effects of Na+ replacement and amiloride on ursodeoxycholic acid-stimulated choleresis and biliary bicarbonate secretion. Am J Physiol. 1987 Feb;252(2 Pt 1):G163–G169. doi: 10.1152/ajpgi.1987.252.2.G163. [DOI] [PubMed] [Google Scholar]
  20. Layden T. J., Boyer J. L. The effect of thyroid hormone on bile salt-independent bile flow and Na+, K+ -ATPase activity in liver plasma membranes enriched in bile canaliculi. J Clin Invest. 1976 Apr;57(4):1009–1018. doi: 10.1172/JCI108342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mahnensmith R. L., Aronson P. S. The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circ Res. 1985 Jun;56(6):773–788. doi: 10.1161/01.res.56.6.773. [DOI] [PubMed] [Google Scholar]
  22. Meier P. J., Knickelbein R., Moseley R. H., Dobbins J. W., Boyer J. L. Evidence for carrier-mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles. J Clin Invest. 1985 Apr;75(4):1256–1263. doi: 10.1172/JCI111824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meier P. J., Sztul E. S., Reuben A., Boyer J. L. Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver. J Cell Biol. 1984 Mar;98(3):991–1000. doi: 10.1083/jcb.98.3.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miner P. B., Jr, Sutherland E., Simon F. R. Regulation of hepatic sodium plus potassium-activated adenossine triphosphatase activity by glucocorticoids in the rat. Gastroenterology. 1980 Aug;79(2):212–221. [PubMed] [Google Scholar]
  25. Moseley R. H., Boyer J. L. Mechanisms of electrolyte transport in the liver and their functional significance. Semin Liver Dis. 1985 May;5(2):122–135. doi: 10.1055/s-2008-1063917. [DOI] [PubMed] [Google Scholar]
  26. Reichen J., Paumgartner G. Uptake of bile acids by perfused rat liver. Am J Physiol. 1976 Sep;231(3):734–742. doi: 10.1152/ajplegacy.1976.231.3.734. [DOI] [PubMed] [Google Scholar]
  27. Scharschmidt B. F., Keeffe E. B., Vessey D. A., Blankenship N. M., Ockner R. K. In vitro effect of bile salts on rat liver plasma membrane, lipid fluidity, and ATPase activity. Hepatology. 1981 Mar-Apr;1(2):137–145. doi: 10.1002/hep.1840010209. [DOI] [PubMed] [Google Scholar]
  28. Scharschmidt B. F., Stephens J. E. Transport of sodium, chloride, and taurocholate by cultured rat hepatocytes. Proc Natl Acad Sci U S A. 1981 Feb;78(2):986–990. doi: 10.1073/pnas.78.2.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scharschmidt B. F., Van Dyke R. W. Mechanisms of hepatic electrolyte transport. Gastroenterology. 1983 Nov;85(5):1199–1214. [PubMed] [Google Scholar]
  30. Shinitzky M., Barenholz Y. Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta. 1978 Dec 15;515(4):367–394. doi: 10.1016/0304-4157(78)90010-2. [DOI] [PubMed] [Google Scholar]
  31. Van Dyke R. W., Stephens J. E., Scharschmidt B. F. Bile acid transport in cultured rat hepatocytes. Am J Physiol. 1982 Dec;243(6):G484–G492. doi: 10.1152/ajpgi.1982.243.6.G484. [DOI] [PubMed] [Google Scholar]
  32. Van Dyke R. W., Stephens J. E., Scharschmidt B. F. Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver. J Clin Invest. 1982 Sep;70(3):505–517. doi: 10.1172/JCI110642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wannagat R. J., Adler R. D., Ockner R. K. Bile acid-induced increase in bile acid-independent flow and plasma membrane NaK-ATPase activity in rat liver. J Clin Invest. 1978 Feb;61(2):297–307. doi: 10.1172/JCI108939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weinberg S. L., Burckhardt G., Wilson F. A. Taurocholate transport by rat intestinal basolateral membrane vesicles. Evidence for the presence of an anion exchange transport system. J Clin Invest. 1986 Jul;78(1):44–50. doi: 10.1172/JCI112571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zouboulis-Vafiadis I., Dumont M., Erlinger S. Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat. Am J Physiol. 1982 Sep;243(3):G208–G213. doi: 10.1152/ajpgi.1982.243.3.G208. [DOI] [PubMed] [Google Scholar]

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

RESOURCES