Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity

Autores
Yeves, Alejandra del Milagro; Garciarena, Carolina Denis; Nolly, Mariela Beatriz; Chiappe, Gladys Ethel; Cingolani, Horacio Eugenio; Ennis, Irene Lucia
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The beneficial effect of phosphodiesterase 5A inhibition in ischemia/reperfusion injury and cardiac hypertrophy is well established. Inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1) exerts beneficial effects on these same conditions, and a possible link between these therapeutic strategies was suggested. Experiments were performed in isolated cat cardiomyocytes to gain insight into the intracellular pathway involved in the reduction of NHE-1 activity by phosphodiesterase 5A inhibition. NHE-1 activity was assessed by the rate of intracellular pH recovery from a sustained acidic load in the absence of bicarbonate. Phosphodiesterase 5A inhibition with sildenafil (1 μmol/L) did not affect basal intracellular pH; yet, it did decrease proton efflux (J(H); in millimoles per liter per minute) after the acidic load (proton efflux: 6.97±0.43 in control versus 3.31±0.58 with sildenafil; P<0.05). The blockade of both protein phosphatase 1 and 2A with 100 nmol/L of okadaic acid reverted the sildenafil effect (proton efflux: 6.77±0.82). In contrast, selective inhibition of protein phosphatase 2A (1 nmol/L of okadaic acid or 100 μmol/L of endothall) did not (3.86±1.0 and 2.61±1.2), suggesting that only protein phosphatase 1 was involved in sildenafil-induced NHE-1 inhibition. Moreover, sildenafil prevented the acidosis-induced increase in NHE-1 phosphorylation without affecting activation of the extracellular signal-regulated kinase 1/2-p90(RSK) pathway. Our results suggest that phosphodiesterase 5A inhibition decreases NHE-1 activity, during intracellular pH recovery after an acidic load, by a protein phosphatase 1-dependent reduction in NHE-1 phosphorylation.
Fil: Yeves, Alejandra del Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Garciarena, Carolina Denis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Nolly, Mariela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Chiappe, Gladys Ethel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Materia
Intracellular Acidosis
Ion Transport
Phosphatases
Phosphorylation
Signal Transduction
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:11336/61848
Acceder
id CONICETDig_8120a1da38881ae256d98f0aece4e978
oai_identifier_str oai:ri.conicet.gov.ar:11336/61848
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activityYeves, Alejandra del MilagroGarciarena, Carolina DenisNolly, Mariela BeatrizChiappe, Gladys EthelCingolani, Horacio EugenioEnnis, Irene LuciaIntracellular AcidosisIon TransportPhosphatasesPhosphorylationSignal Transductionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The beneficial effect of phosphodiesterase 5A inhibition in ischemia/reperfusion injury and cardiac hypertrophy is well established. Inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1) exerts beneficial effects on these same conditions, and a possible link between these therapeutic strategies was suggested. Experiments were performed in isolated cat cardiomyocytes to gain insight into the intracellular pathway involved in the reduction of NHE-1 activity by phosphodiesterase 5A inhibition. NHE-1 activity was assessed by the rate of intracellular pH recovery from a sustained acidic load in the absence of bicarbonate. Phosphodiesterase 5A inhibition with sildenafil (1 μmol/L) did not affect basal intracellular pH; yet, it did decrease proton efflux (J(H); in millimoles per liter per minute) after the acidic load (proton efflux: 6.97±0.43 in control versus 3.31±0.58 with sildenafil; P<0.05). The blockade of both protein phosphatase 1 and 2A with 100 nmol/L of okadaic acid reverted the sildenafil effect (proton efflux: 6.77±0.82). In contrast, selective inhibition of protein phosphatase 2A (1 nmol/L of okadaic acid or 100 μmol/L of endothall) did not (3.86±1.0 and 2.61±1.2), suggesting that only protein phosphatase 1 was involved in sildenafil-induced NHE-1 inhibition. Moreover, sildenafil prevented the acidosis-induced increase in NHE-1 phosphorylation without affecting activation of the extracellular signal-regulated kinase 1/2-p90(RSK) pathway. Our results suggest that phosphodiesterase 5A inhibition decreases NHE-1 activity, during intracellular pH recovery after an acidic load, by a protein phosphatase 1-dependent reduction in NHE-1 phosphorylation.Fil: Yeves, Alejandra del Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Garciarena, Carolina Denis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Nolly, Mariela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Chiappe, Gladys Ethel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaLippincott Williams2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/61848Yeves, Alejandra del Milagro; Garciarena, Carolina Denis; Nolly, Mariela Beatriz; Chiappe, Gladys Ethel; Cingolani, Horacio Eugenio; et al.; Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity; Lippincott Williams; Hypertension; 56; 4; 10-2010; 690-6950194-911XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/abs/10.1161/hypertensionaha.110.151324info:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.110.151324info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:29:00Zoai:ri.conicet.gov.ar:11336/61848instacron: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:34982025-10-22 11:29:00.444CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
title Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
spellingShingle Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
Yeves, Alejandra del Milagro
Intracellular Acidosis
Ion Transport
Phosphatases
Phosphorylation
Signal Transduction
title_short Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
title_full Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
title_fullStr Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
title_full_unstemmed Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
title_sort Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
dc.creator.none.fl_str_mv Yeves, Alejandra del Milagro
Garciarena, Carolina Denis
Nolly, Mariela Beatriz
Chiappe, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucia
author Yeves, Alejandra del Milagro
author_facet Yeves, Alejandra del Milagro
Garciarena, Carolina Denis
Nolly, Mariela Beatriz
Chiappe, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucia
author_role author
author2 Garciarena, Carolina Denis
Nolly, Mariela Beatriz
Chiappe, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Intracellular Acidosis
Ion Transport
Phosphatases
Phosphorylation
Signal Transduction
topic Intracellular Acidosis
Ion Transport
Phosphatases
Phosphorylation
Signal Transduction
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 beneficial effect of phosphodiesterase 5A inhibition in ischemia/reperfusion injury and cardiac hypertrophy is well established. Inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1) exerts beneficial effects on these same conditions, and a possible link between these therapeutic strategies was suggested. Experiments were performed in isolated cat cardiomyocytes to gain insight into the intracellular pathway involved in the reduction of NHE-1 activity by phosphodiesterase 5A inhibition. NHE-1 activity was assessed by the rate of intracellular pH recovery from a sustained acidic load in the absence of bicarbonate. Phosphodiesterase 5A inhibition with sildenafil (1 μmol/L) did not affect basal intracellular pH; yet, it did decrease proton efflux (J(H); in millimoles per liter per minute) after the acidic load (proton efflux: 6.97±0.43 in control versus 3.31±0.58 with sildenafil; P<0.05). The blockade of both protein phosphatase 1 and 2A with 100 nmol/L of okadaic acid reverted the sildenafil effect (proton efflux: 6.77±0.82). In contrast, selective inhibition of protein phosphatase 2A (1 nmol/L of okadaic acid or 100 μmol/L of endothall) did not (3.86±1.0 and 2.61±1.2), suggesting that only protein phosphatase 1 was involved in sildenafil-induced NHE-1 inhibition. Moreover, sildenafil prevented the acidosis-induced increase in NHE-1 phosphorylation without affecting activation of the extracellular signal-regulated kinase 1/2-p90(RSK) pathway. Our results suggest that phosphodiesterase 5A inhibition decreases NHE-1 activity, during intracellular pH recovery after an acidic load, by a protein phosphatase 1-dependent reduction in NHE-1 phosphorylation.
Fil: Yeves, Alejandra del Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Garciarena, Carolina Denis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Nolly, Mariela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Chiappe, Gladys Ethel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares ; Argentina
description The beneficial effect of phosphodiesterase 5A inhibition in ischemia/reperfusion injury and cardiac hypertrophy is well established. Inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1) exerts beneficial effects on these same conditions, and a possible link between these therapeutic strategies was suggested. Experiments were performed in isolated cat cardiomyocytes to gain insight into the intracellular pathway involved in the reduction of NHE-1 activity by phosphodiesterase 5A inhibition. NHE-1 activity was assessed by the rate of intracellular pH recovery from a sustained acidic load in the absence of bicarbonate. Phosphodiesterase 5A inhibition with sildenafil (1 μmol/L) did not affect basal intracellular pH; yet, it did decrease proton efflux (J(H); in millimoles per liter per minute) after the acidic load (proton efflux: 6.97±0.43 in control versus 3.31±0.58 with sildenafil; P<0.05). The blockade of both protein phosphatase 1 and 2A with 100 nmol/L of okadaic acid reverted the sildenafil effect (proton efflux: 6.77±0.82). In contrast, selective inhibition of protein phosphatase 2A (1 nmol/L of okadaic acid or 100 μmol/L of endothall) did not (3.86±1.0 and 2.61±1.2), suggesting that only protein phosphatase 1 was involved in sildenafil-induced NHE-1 inhibition. Moreover, sildenafil prevented the acidosis-induced increase in NHE-1 phosphorylation without affecting activation of the extracellular signal-regulated kinase 1/2-p90(RSK) pathway. Our results suggest that phosphodiesterase 5A inhibition decreases NHE-1 activity, during intracellular pH recovery after an acidic load, by a protein phosphatase 1-dependent reduction in NHE-1 phosphorylation.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/61848
Yeves, Alejandra del Milagro; Garciarena, Carolina Denis; Nolly, Mariela Beatriz; Chiappe, Gladys Ethel; Cingolani, Horacio Eugenio; et al.; Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity; Lippincott Williams; Hypertension; 56; 4; 10-2010; 690-695
0194-911X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/61848
identifier_str_mv Yeves, Alejandra del Milagro; Garciarena, Carolina Denis; Nolly, Mariela Beatriz; Chiappe, Gladys Ethel; Cingolani, Horacio Eugenio; et al.; Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity; Lippincott Williams; Hypertension; 56; 4; 10-2010; 690-695
0194-911X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/abs/10.1161/hypertensionaha.110.151324
info:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.110.151324
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
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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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score 12.982451

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