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

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 sugge...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yeves, Alejandra M., Garciarena, Carolina Denis, Nolly, Mariela, Chiappe de Cingolani, Gladys Ethel, Cingolani, Horacio Eugenio, Ennis, Irene Lucía
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Ciencias Médicas
intracellular acidosis
ion transport
phosphatases
phosphorylation
signal transduction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82617
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82617
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
intracellular acidosis
ion transport
phosphatases
phosphorylation
signal transduction
spellingShingle Ciencias Médicas
intracellular acidosis
ion transport
phosphatases
phosphorylation
signal transduction
Yeves, Alejandra M.
Garciarena, Carolina Denis
Nolly, Mariela
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
topic_facet Ciencias Médicas
intracellular acidosis
ion transport
phosphatases
phosphorylation
signal transduction
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 (JH; 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 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.
format Articulo
Articulo
author Yeves, Alejandra M.
Garciarena, Carolina Denis
Nolly, Mariela
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
author_facet Yeves, Alejandra M.
Garciarena, Carolina Denis
Nolly, Mariela
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
author_sort Yeves, Alejandra M.
title Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity
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
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/82617
work_keys_str_mv AT yevesalejandram decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
AT garciarenacarolinadenis decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
AT nollymariela decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
AT chiappedecingolanigladysethel decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
AT cingolanihoracioeugenio decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
AT ennisirenelucia decreasedactivityofthenahexchangerbyphosphodiesterase5ainhibitionisattributedtoanincreaseinproteinphosphataseactivity
bdutipo_str Repositorios
_version_ 1764820488451784708

Ejemplares similares