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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/120606
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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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1844613110993780736 |
score |
13.070432 |