8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A

Autores
Cabral, Pablo D.; Silva, Guillermo Benjamin; Baigorria, Sandra T.; Juncos, Luis A.; Juncos, Luis I.; Garcia, Nestor Horacio
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2á (8-iso-PGF2á) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2á regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2á increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2á on NaCl transport by measuring chloride absorption (J Cl) in isolated microperfused cTALs. Adding 8-iso-PGF2á to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min-1·mm-1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min-1·mm -1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min-1·mm-1, and 8-iso-PGF2á raised it to 35.1 ± 1.4 fmol·min -1·mm-1, an increase of 94% (P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 ìM), 8-iso-PGF2á failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min -1·mm-1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min-1·mm-1; NS). We concluded that 8-iso-PGF2á stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.
Fil: Cabral, Pablo D.. Henry Ford Hospital; Estados Unidos
Fil: Silva, Guillermo Benjamin. Universidad Nacional de San Juan. Facultad de Ingeniería. Departamento de Electrónica y Automática. Gabinete de Tecnología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baigorria, Sandra T.. Fundación J. Robert Cade; Argentina
Fil: Juncos, Luis A.. University of Mississippi; Estados Unidos
Fil: Juncos, Luis I.. University of Mississippi; Estados Unidos
Fil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Materia
Cortico-medullary osmotic gradient
Salt reabsorption
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/191432

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network_name_str CONICET Digital (CONICET)
spelling 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase ACabral, Pablo D.Silva, Guillermo BenjaminBaigorria, Sandra T.Juncos, Luis A.Juncos, Luis I.Garcia, Nestor HoracioCortico-medullary osmotic gradientSalt reabsorptionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2á (8-iso-PGF2á) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2á regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2á increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2á on NaCl transport by measuring chloride absorption (J Cl) in isolated microperfused cTALs. Adding 8-iso-PGF2á to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min-1·mm-1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min-1·mm -1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min-1·mm-1, and 8-iso-PGF2á raised it to 35.1 ± 1.4 fmol·min -1·mm-1, an increase of 94% (P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 ìM), 8-iso-PGF2á failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min -1·mm-1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min-1·mm-1; NS). We concluded that 8-iso-PGF2á stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.Fil: Cabral, Pablo D.. Henry Ford Hospital; Estados UnidosFil: Silva, Guillermo Benjamin. Universidad Nacional de San Juan. Facultad de Ingeniería. Departamento de Electrónica y Automática. Gabinete de Tecnología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baigorria, Sandra T.. Fundación J. Robert Cade; ArgentinaFil: Juncos, Luis A.. University of Mississippi; Estados UnidosFil: Juncos, Luis I.. University of Mississippi; Estados UnidosFil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaAmerican Physiological Society2010-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/191432Cabral, Pablo D.; Silva, Guillermo Benjamin; Baigorria, Sandra T.; Juncos, Luis A.; Juncos, Luis I.; et al.; 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A; American Physiological Society; AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY - (Print); 299; 6; 1-12-2010; 1396-14000363-6127CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00225.2010info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajprenal.00225.2010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:12:56Zoai:ri.conicet.gov.ar:11336/191432instacron: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 10:12:56.821CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
title 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
spellingShingle 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
Cabral, Pablo D.
Cortico-medullary osmotic gradient
Salt reabsorption
title_short 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
title_full 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
title_fullStr 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
title_full_unstemmed 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
title_sort 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A
dc.creator.none.fl_str_mv Cabral, Pablo D.
Silva, Guillermo Benjamin
Baigorria, Sandra T.
Juncos, Luis A.
Juncos, Luis I.
Garcia, Nestor Horacio
author Cabral, Pablo D.
author_facet Cabral, Pablo D.
Silva, Guillermo Benjamin
Baigorria, Sandra T.
Juncos, Luis A.
Juncos, Luis I.
Garcia, Nestor Horacio
author_role author
author2 Silva, Guillermo Benjamin
Baigorria, Sandra T.
Juncos, Luis A.
Juncos, Luis I.
Garcia, Nestor Horacio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cortico-medullary osmotic gradient
Salt reabsorption
topic Cortico-medullary osmotic gradient
Salt reabsorption
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2á (8-iso-PGF2á) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2á regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2á increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2á on NaCl transport by measuring chloride absorption (J Cl) in isolated microperfused cTALs. Adding 8-iso-PGF2á to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min-1·mm-1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min-1·mm -1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min-1·mm-1, and 8-iso-PGF2á raised it to 35.1 ± 1.4 fmol·min -1·mm-1, an increase of 94% (P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 ìM), 8-iso-PGF2á failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min -1·mm-1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min-1·mm-1; NS). We concluded that 8-iso-PGF2á stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.
Fil: Cabral, Pablo D.. Henry Ford Hospital; Estados Unidos
Fil: Silva, Guillermo Benjamin. Universidad Nacional de San Juan. Facultad de Ingeniería. Departamento de Electrónica y Automática. Gabinete de Tecnología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baigorria, Sandra T.. Fundación J. Robert Cade; Argentina
Fil: Juncos, Luis A.. University of Mississippi; Estados Unidos
Fil: Juncos, Luis I.. University of Mississippi; Estados Unidos
Fil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
description Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2á (8-iso-PGF2á) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2á regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2á increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2á on NaCl transport by measuring chloride absorption (J Cl) in isolated microperfused cTALs. Adding 8-iso-PGF2á to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min-1·mm-1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min-1·mm -1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min-1·mm-1, and 8-iso-PGF2á raised it to 35.1 ± 1.4 fmol·min -1·mm-1, an increase of 94% (P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 ìM), 8-iso-PGF2á failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min -1·mm-1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min-1·mm-1; NS). We concluded that 8-iso-PGF2á stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.
publishDate 2010
dc.date.none.fl_str_mv 2010-12-01
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/11336/191432
Cabral, Pablo D.; Silva, Guillermo Benjamin; Baigorria, Sandra T.; Juncos, Luis A.; Juncos, Luis I.; et al.; 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A; American Physiological Society; AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY - (Print); 299; 6; 1-12-2010; 1396-1400
0363-6127
CONICET Digital
CONICET
url http://hdl.handle.net/11336/191432
identifier_str_mv Cabral, Pablo D.; Silva, Guillermo Benjamin; Baigorria, Sandra T.; Juncos, Luis A.; Juncos, Luis I.; et al.; 8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: Role of cAMP and protein kinase A; American Physiological Society; AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY - (Print); 299; 6; 1-12-2010; 1396-1400
0363-6127
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00225.2010
info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajprenal.00225.2010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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