Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow

Autores
Marinelli, Raul Alberto; Vore, Mary; Javitt, Norman B.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The purpose of this minireview is to show that a new paradigm is developing regarding hepatic bile flow. The focus thus far has been on carrier-mediated transport of bile acids and other solutes, such as glutathione, which create an osmotic gradient for the transcellular and paracellular flow of water into canaliculi. In addition to the physicochemical properties of bile acids, which govern the osmotic gradient, data now exist showing that the tight junctions governing paracellular water flow and Aquaporin-8 water channels governing transcellular water flow are regulated independently. Thus, the rate of water flow into the canaliculus in response to bile acid transport is variable and determines canalicular bile acid concentration, which affects the production and solubilization of cholesterol-lecithin vesicles. These new considerations modify thinking regarding the occurrence of cholestasis and its progression and reorient the design of experimental studies that can distinguish the different determinants of bile flow. SIGNIFICANCE STATEMENT The paradigm that water flow into the canaliculus is determined only by the rate of carrier-mediated transport has been challenged recently by the changes that occur in hepatic bile composition in the Claudin-2 knockout mouse and with the cholestatic effect of estradiol 17b-D-glucuronide. Thus, a respective reduction in paracellular or transcellular canalicular water flow, probably via Aquaporin 8, has no significant effect on bile acid excretion.
Fil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Vore, Mary. University of Kentucky; Estados Unidos
Fil: Javitt, Norman B.. University of New York. School of Medicine; Estados Unidos
Materia
Canalicular bile
Water flow
Aquaporin-8
Estradiol 17b-D-glucuronide
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120606

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spelling Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flowMarinelli, Raul AlbertoVore, MaryJavitt, Norman B.Canalicular bileWater flowAquaporin-8Estradiol 17b-D-glucuronidehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The purpose of this minireview is to show that a new paradigm is developing regarding hepatic bile flow. The focus thus far has been on carrier-mediated transport of bile acids and other solutes, such as glutathione, which create an osmotic gradient for the transcellular and paracellular flow of water into canaliculi. In addition to the physicochemical properties of bile acids, which govern the osmotic gradient, data now exist showing that the tight junctions governing paracellular water flow and Aquaporin-8 water channels governing transcellular water flow are regulated independently. Thus, the rate of water flow into the canaliculus in response to bile acid transport is variable and determines canalicular bile acid concentration, which affects the production and solubilization of cholesterol-lecithin vesicles. These new considerations modify thinking regarding the occurrence of cholestasis and its progression and reorient the design of experimental studies that can distinguish the different determinants of bile flow. SIGNIFICANCE STATEMENT The paradigm that water flow into the canaliculus is determined only by the rate of carrier-mediated transport has been challenged recently by the changes that occur in hepatic bile composition in the Claudin-2 knockout mouse and with the cholestatic effect of estradiol 17b-D-glucuronide. Thus, a respective reduction in paracellular or transcellular canalicular water flow, probably via Aquaporin 8, has no significant effect on bile acid excretion.Fil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Vore, Mary. University of Kentucky; Estados UnidosFil: Javitt, Norman B.. University of New York. School of Medicine; Estados UnidosAmerican Society for Pharmacology and Experimental Therapeutics2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120606Marinelli, Raul Alberto; Vore, Mary; Javitt, Norman B.; Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 371; 3; 12-2019; 713-7170022-3565CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1124/jpet.119.261115info:eu-repo/semantics/altIdentifier/url/https://jpet.aspetjournals.org/content/371/3/713info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:37Zoai:ri.conicet.gov.ar:11336/120606instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:35:38.142CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
title Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
spellingShingle Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
Marinelli, Raul Alberto
Canalicular bile
Water flow
Aquaporin-8
Estradiol 17b-D-glucuronide
title_short Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
title_full Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
title_fullStr Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
title_full_unstemmed Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
title_sort Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow
dc.creator.none.fl_str_mv Marinelli, Raul Alberto
Vore, Mary
Javitt, Norman B.
author Marinelli, Raul Alberto
author_facet Marinelli, Raul Alberto
Vore, Mary
Javitt, Norman B.
author_role author
author2 Vore, Mary
Javitt, Norman B.
author2_role author
author
dc.subject.none.fl_str_mv Canalicular bile
Water flow
Aquaporin-8
Estradiol 17b-D-glucuronide
topic Canalicular bile
Water flow
Aquaporin-8
Estradiol 17b-D-glucuronide
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The purpose of this minireview is to show that a new paradigm is developing regarding hepatic bile flow. The focus thus far has been on carrier-mediated transport of bile acids and other solutes, such as glutathione, which create an osmotic gradient for the transcellular and paracellular flow of water into canaliculi. In addition to the physicochemical properties of bile acids, which govern the osmotic gradient, data now exist showing that the tight junctions governing paracellular water flow and Aquaporin-8 water channels governing transcellular water flow are regulated independently. Thus, the rate of water flow into the canaliculus in response to bile acid transport is variable and determines canalicular bile acid concentration, which affects the production and solubilization of cholesterol-lecithin vesicles. These new considerations modify thinking regarding the occurrence of cholestasis and its progression and reorient the design of experimental studies that can distinguish the different determinants of bile flow. SIGNIFICANCE STATEMENT The paradigm that water flow into the canaliculus is determined only by the rate of carrier-mediated transport has been challenged recently by the changes that occur in hepatic bile composition in the Claudin-2 knockout mouse and with the cholestatic effect of estradiol 17b-D-glucuronide. Thus, a respective reduction in paracellular or transcellular canalicular water flow, probably via Aquaporin 8, has no significant effect on bile acid excretion.
Fil: Marinelli, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina
Fil: Vore, Mary. University of Kentucky; Estados Unidos
Fil: Javitt, Norman B.. University of New York. School of Medicine; Estados Unidos
description The purpose of this minireview is to show that a new paradigm is developing regarding hepatic bile flow. The focus thus far has been on carrier-mediated transport of bile acids and other solutes, such as glutathione, which create an osmotic gradient for the transcellular and paracellular flow of water into canaliculi. In addition to the physicochemical properties of bile acids, which govern the osmotic gradient, data now exist showing that the tight junctions governing paracellular water flow and Aquaporin-8 water channels governing transcellular water flow are regulated independently. Thus, the rate of water flow into the canaliculus in response to bile acid transport is variable and determines canalicular bile acid concentration, which affects the production and solubilization of cholesterol-lecithin vesicles. These new considerations modify thinking regarding the occurrence of cholestasis and its progression and reorient the design of experimental studies that can distinguish the different determinants of bile flow. SIGNIFICANCE STATEMENT The paradigm that water flow into the canaliculus is determined only by the rate of carrier-mediated transport has been challenged recently by the changes that occur in hepatic bile composition in the Claudin-2 knockout mouse and with the cholestatic effect of estradiol 17b-D-glucuronide. Thus, a respective reduction in paracellular or transcellular canalicular water flow, probably via Aquaporin 8, has no significant effect on bile acid excretion.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120606
Marinelli, Raul Alberto; Vore, Mary; Javitt, Norman B.; Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 371; 3; 12-2019; 713-717
0022-3565
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120606
identifier_str_mv Marinelli, Raul Alberto; Vore, Mary; Javitt, Norman B.; Hepatic bile formation: Canalicular osmolarity and paracellular and transcellular water flow; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 371; 3; 12-2019; 713-717
0022-3565
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1124/jpet.119.261115
info:eu-repo/semantics/altIdentifier/url/https://jpet.aspetjournals.org/content/371/3/713
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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