BASES MOLECULARES DE LA FUNCION EXCRETORA DE TIPO HEPATOBILIAR DE LA PLACENTA

(especial para SIIC © Derechos reservados)
La vía mayoritaria en la transferencia placentaria de ácidos biliares y bilirrubina está mediada por sistemas de transporte que, en conjunto, presentan características de vectorialidad feto-materna, y que también juegan un papel en la barrera placentaria reduciendo el flujo de sustancias nocivas desde la madre al feto.
marin9.jpg Autor:
Marín, josé j g
Columnista Experto de SIIC

Institución:
Departamento de Fisiología y Farmacología Universidad de Salamanca Salamanca, España


Artículos publicados por Marín, josé j g
Coautores
Rocío I. R. Macías*  Oscar Briz**  M. Angeles Serrano*** 
Departamento de Fisiología, Universidad de Salamanca, Salamanca, España*
Departamentos de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, España**
Departamentos de Bioquímica y Biología Molecular, Universidad de Salamanca, Salamanca, España***
Recepción del artículo
30 de Agosto, 2004
Aprobación
12 de Octubre, 2004
Primera edición
18 de Febrero, 2005
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
El hígado juega un papel determinante en la excreción de sustancias potencialmente tóxicas de origen externo o producidas por el organismo, como ácidos biliares y bilirrubina. Esta función implica tanto procesos de transporte como de biotransformación. Durante la vida intrauterina, el hígado fetal no es aún capaz de realizar esta función, por lo que es la placenta la que asume un papel excretor similar al que desempeña el sistema hepatobiliar en el adulto. La similitud entre ambas funciones se debe a la presencia en ambos órganos de proteínas transportadoras de la familia OATP, que llevan a cabo la captación de aniones orgánicos en varios epitelios, y de miembros de la superfamilia de proteínas ABC ("ATP-binding cassette"), capaces de bombear al exterior celular una gran variedad de sustancias. Estudios recientes demostraron que, además de un componente difusional, que es más relevante en el caso de la bilirrubina no conjugada, la vía mayoritaria en la transferencia placentaria de ácidos biliares y bilirrubina está mediada por sistemas de transporte que, en conjunto, presentan características de vectorialidad feto-materna, y que por ello también juegan un papel en la barrera placentaria reduciendo el flujo de sustancias nocivas desde la madre al feto.

Palabras clave
Acidos biliares, aniones colefílicos, bilirrubina, biliverdina, feto, gestación, hígado, trofoblasto


Artículo completo

(castellano)
Extensión:  +/-5.19 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
The liver plays an important excretory role eliminating from the body potentially toxic compounds that are xenobiotics or produced endogenously, such as bile acids and biliary pigments. This involves both transport and biotransformation processes. During intrauterine life, the inmature fetal liver cannot carry out this function. Therefore, the placenta performs a hepatobiliary-like excretory role, transferring cholephilic compounds from the fetus to the mother. The similarity of this function in the placenta and the adult liver is probably accounted for by the presence in both organs of proteins of the OATP family, involved in the uptake of organic anions across the basolateral membrane of several epithelia, and of members of the superfamily of ATP-binding cassette (ABC) proteins, which are involved in the export of substances out of many different cells. Thus, several studies have shown that, in addition to a difussional component, that may become particularly important for unconjugated bilirubin, the main mechanisms for bile acids and bilirubin transplacental transfer from the fetus to the mother are carrier-mediated transport systems, which have vectorial properties and also play an important role in the placental barrier by preventing or reducing the net flux of noxious substances from the mother to the fetus.

Key words
Bile acids, cholephilics anions, bilirubin, biliverdin, fetus, liver, trophoblast


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Obstetricia y Ginecología
Relacionadas: Bioquímica, Farmacología, Gastroenterología, Pediatría



Comprar este artículo
Extensión: 5.19 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Marín, José J G
Bibliografía del artículo
  1. Vavricka SR, Van Montfoort J, Ha HR y col. (2002) Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology 36, 164-172.
  2. Zucker SD y Goessling W. (2000) Mechanism of hepatocellular uptake of albumin-bound bilirubin. Biochim Biophys Acta 1464, 7-17.
  3. Meier PJ y Stieger B. (2002) Bile salt transporters. Annu Rev Physiol 64, 635-661.
  4. Ferenci P, Zollner G y Trauner M. (2002) Hepatic transport systems. J Gastroenterol Hepatol 17, S105-S112.
  5. Briz O, Serrano MA, Macías RIR y col. (2003) Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8 in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J 371, 897-905.
  6. Craddock AL, Love MW, Daniel RW y col. (1998) Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol 37, G157-G169.
  7. Suzuki H y Sugiyama Y. (2000) Transport of drugs across the hepatic sinusoidal membrane: sinusoidal drug influx and efflux in the liver. Semin Liver Dis 20, 251-263.
  8. Kekuda R, Prasad PD, Wu X y col. (1998) Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem 273, 15971-15979.
  9. Muller M, Mayer R, Hero U y col. (1994) ATP-dependent transport of amphiphilic cations across the hepatocyte canalicular membrane mediated by Mdr1 P-glycoprotein. FEBS Lett 343, 168-172.
  10. Jedlitschky G, Leier I, Buchholz U y col. (1997) ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem J 327, 305-310.
  11. Ogawa K, Suzuki H, Hirohashi T y col. (2000) Characterization of inducible nature of MRP3 in rat liver. Am J Physiol 278, G438-G446.
  12. Soroka CJ, Lee JM, Azzaroli F y col. (2001) Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 33, 783-791.
  13. Donner MG y Keppler D. (2001) Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Hepatology 34, 351-359.
  14. Vos TA, Hooiveld GJ, Koning H y col. (1998) Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver. Hepatology 28, 1637-1644.
  15. Tanaka Y, Kobayashi Y, Gabazza EC y col. (2002) Increased renal expression of bilirubin glucuronide transporters in a rat model of obstructive jaundice. Am J Physiol 282, G656-G662.
  16. Marín JJG, Briz O y Serrano MA. (2004) A review on the molecular mechanisms involved in the placental barrier for drugs. Current Drug Delivery 1, 275-289.
  17. Javitt NB. (2002) Cholesterol, hydroxycholesterols, and bile acids. Biochem Biophys Res Commun 292, 1147-1153.
  18. Colombo C, Roda A, Roda E y col. (1985) Correlation between fetal and maternal serum bile acid concentrations. Pediatr Res 19, 227-231.
  19. Balistreri WF, Kader HHA, Setchell KDR y col. (1992) New methods for assessing liver function in infants and children. Ann Clin Lab Sci 22, 162-174.
  20. Nakagawa M y Setchell KDR. (1990) Bile acid metabolism in early life: Studies of amniotic fluid. J Lipid Res 31, 1089-1098.
  21. Monte MJ, Rodriguez-Bravo T, Macías RIR y col. (1995) Relationship between bile acid transplacental gradients and transport across the fetal-facing plasma membrane of the human trophoblast. Pediatr Res 38, 156-163.
  22. Cabral DJ, Small DM, Lilly HS y col. (1987) Transbilayer movement of bile acids in model membranes. Biochemistry 26, 1801-1804.
  23. Macías RIR, Pascual MJ, Bravo A y col. (2000) Effect of maternal cholestasis on bile acid transfer across the placenta-maternal liver tandem. Hepatology 31, 975-983.
  24. Marín JJG, Serrano MA, El-Mir MY y col. (1990) Bile acid transport by basal membrane vesicles of human term placental trophoblast. Gastroenterology 99, 1431-1438.
  25. El-Mir MY, Eleno N, Serrano MA y col. (1991) Bicarbonate-induced activation of taurocholate transport across the basal plasma membrane of the human term trophoblast. Am J Physiol 260, G887-G894.
  26. Serrano MA, Bravo P, El-Mir MY y col. (1993) Influence of hydroxylation and conjugation in cross-inhibition of bile acid transport across the human trophoblast basal membrane. Biochim Biophys Acta 1151, 28-34.
  27. Bravo P, El-Mir MYA, Serrano MA y col. (1993) Interaction between cholephilic anions and bile acid transport across basal membrane of human trophoblast. Am J Physiol 265, G242-G250.
  28. Serrano MA, Macías RIR, Vallejo M y col. (2003) Effect of ursodeoxycholic acid on the impairment induced by maternal cholestasis in the rat placenta-maternal liver tandem excretory pathway. J Pharmacol Exp Therap 305, 515-524.
  29. Marín JJG, Bravo P, El-Mir MY y col. (1995) ATP-dependent bile acid transport across microvillous membrane of human term trophoblast. Am J Physiol 268, G685-G694.
  30. Bravo P, Marín JJG, Beveridge MJ y col. (1995) Reconstitution and characterization of ATP-dependent bile acid transport in human and rat placenta. Biochem J 311, 479-485.
  31. Dumaswala R, Setchell KDR, Moyer MS y col. (1993) An anion exchanger mediates bile acid transport across the placental microvillous membrane. Am J Physiol 264, G1016-G1023.
  32. Iioka H, Hisanaga H, Akada S y col. (1993) Characterization of human placental activity for transport of taurocholate, using brush border (microvillous) membrane vesicles. Placenta 14, 93-102.
  33. St-Pierre MV, Serrano MA, Macías RIR y col. (2000) Expression of members of the multidrug resistance protein family in human term placenta. Am J Physiol 279, R1495-R1503.
  34. Goodwin B y Kliewer SA. (2002) Nuclear receptors I. Nuclear receptors and bile acid homeostasis. Am J Physiol 282, G926-G931.
  35. Galbraith R. (1999) Heme oxygenase: who needs it Proc Soc Exp Biol Med 222, 299-305.
  36. Ryter SW y Tyrrell RM. (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. Free Radic Biol Med 28, 289-309.
  37. McCoubrey WK, Cooklis MA y Maines MD. (1995) The structure, organization and differential expression of the rat gene encoding biliverdin reductase. Gene 160, 235-240.
  38. McDonagh AF, Palma LA y Schmid R. (1981) Reduction of biliverdin and placental transfer of bilirubin and biliverdin in the pregnant guinea pig. Biochem J 194, 273-282.
  39. Bosma PJ, Seppen J, Goldhoorn B y col. (1994) Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 269, 17960-17964.
  40. Knudsen A y Lebech M. (1989) Maternal bilirubin, cord bilirubin, and placenta function at delivery and the development of jaundice in mature newborns. Acta Obstet Gynecol Scand 68, 719-724.
  41. Kawade N y Onishi S. (1981) The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 196, 257-260.
  42. McDonagh AF. (2001) Turning green to gold. Nat Struct Biol 8, 198-200.
  43. Serrano MA, Bayón JE, Pascolo L y col. (2002) Evidence for carrier-mediated transport of unconjugated bilirubin across plasma membrane vesicles from human placental trophoblast. Placenta 23, 527-535.
  44. Briz O, Macías RIR, Serrano MA y col. (2003) Excretion of foetal bilirubin by the rat placenta-maternal liver tandem. Placenta 24, 462-472.
  45. Brodie BB, Axelrod J, Soberman R y col. (1949) The estimation of antipyrine in biological materials. J Biol Chem 179, 25-29.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008