title: Effect of maternal obstructive cholestasis during pregnancy on the biliary transport of horseradish peroxidase in the rat offspring.
abstract: MOCP (maternal obstructive cholestasis during pregnancy) induces a reversible impairment in bile formation in young rats born to these mothers. The aim of the present study was to gain information on the effects of MOCP on the maturation of pathways involved in protein secretion into bile in young (4-week-old) rats. The amount of hepatic alpha-tubulin and the structure of the microtubular network were apparently not affected by MOCP. HRP (horseradish peroxidase) was used as a model protein, and its secretion into bile after administration through the jugular vein was measured. In adult (8-week-old) rats, two peaks of HRP output into bile were observed following administration: an early peak presumably due to paracellular transfer, and a late peak presumably due to transcytosis. In young rats (4 weeks old), the early peak was similar to that of adult animals, and was not affected by MOCP. However, the late peak was markedly smaller in young control rats, and was further reduced by MOCP. Brefeldin A decreased, whereas taurocholate did not change, the early peak, whereas both affected the transcytotic transport of HRP. Brefeldin A delayed HRP secretion (similarly in control and MOCP groups), without affecting cumulative output, whereas taurocholate accelerated the transcytotic transport of HRP in the control group, but not in the MOCP group. These results suggest that MOCP affects the maturation of hepatocyte mechanisms involved in the transcytotic secretion of HRP into bile.
authors.affiliation: Departamento de Fisiologia y Farmacologia, Campus Miguel Unamuno, EID-S09, 37007-Salamanca, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Monte
authors.forename: Gloria R
authors.initials: GR
authors.lastname: Villanueva
authors.forename: Rocio I R
authors.initials: RI
authors.lastname: Macias
authors.forename: David J
authors.initials: DJ
authors.lastname: Vazquez
authors.forename: Marta
authors.initials: M
authors.lastname: Toledo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Dominguez
authors.forename: Jose J G
authors.initials: JJ
authors.lastname: Marin
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002779:Cholestasis; D005260:Female; D022781:Hepatocytes / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000378:metabolism*; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D018613:Microscopy, Confocal; D008870:Microtubules / Q000648:ultrastructure; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000494:pharmacology; D013997:Time Factors; D014404:Tubulin / Q000032:analysis
chemical_list: D002756:Cholagogues and Choleretics; D011500:Protein Synthesis Inhibitors; D014404:Tubulin; D020126:Brefeldin A; D013656:Taurocholic Acid; D006735:Horseradish Peroxidase