Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases

Background/Aims: This study aimed to identify the signaling pathway for the proposed link between phosphodiesterase-5A (PDE5A) inhibition and decreased cardiac Na + /H + exchanger (NHE-1) activity. Methods: NHE-1 activity was assessed in rat isolated papillary muscles by the Na + -dependent initial...

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Autores principales: Díaz, Romina Gisel, Nolly, Mariela, Massarutti, Carolina, Casarini, María Jesús, Garciarena, Carolina Denis, Ennis, Irene Lucía, Cingolani, Horacio Eugenio, Pérez, Néstor Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Protein kinase G
Protein phosphatase 2A
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82462
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82462
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
NHE-1
Phosphodiesterase 5A
Protein kinase G
Protein phosphatase 2A
spellingShingle Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Protein kinase G
Protein phosphatase 2A
Díaz, Romina Gisel
Nolly, Mariela
Massarutti, Carolina
Casarini, María Jesús
Garciarena, Carolina Denis
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
topic_facet Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Protein kinase G
Protein phosphatase 2A
description Background/Aims: This study aimed to identify the signaling pathway for the proposed link between phosphodiesterase-5A (PDE5A) inhibition and decreased cardiac Na + /H + exchanger (NHE-1) activity. Methods: NHE-1 activity was assessed in rat isolated papillary muscles by the Na + -dependent initial pH i recovery from a sustained acidosis (ammonium prepulse). ERK1/2, p90RSK and NHE-1 phosphorylation state during acidosis was determined. Results: PDE5A inhibition (1 μmol/L sildenafil, SIL) did not modify basal pH i but significantly blunted pH i recovery after sustained acidosis. Although preventing ERK1/2- p90RSK signaling pathway (10 μmol/L U0126) mimicked SIL effect, SIL did not blunt the acidosis-mediated increase in kinases activation. SIL+U0126 did not show additive effect on NHE-1 activity. Then, we hypothesized that SIL could be activating phophasatases (PP1 and/or PP2A) to directly dephosphorylate NHE-1 despite preserved ERK1/2-p90RSK activation. Non-specific phosphatases inhibition (1 μmol/L okadaic acid) canceled SIL effect on pH i recovery from acidosis. Same result was observed by inhibiting PP2A either with a lower dose of okadaic acid (1 nmol/L) or, more specifically, with 100 μmol/L endothall. Consistently, NHE-1 phosphorylation at Ser703 increased after acidosis, SIL prevented this effect and PP2A inhibition (endothall) reverted SIL effect. Conclusion: We suggest that PDE5A inhibitors decrease NHE-1 phosphorylation and activity through a mechanism that involves PP2A activation.
format Articulo
Articulo
author Díaz, Romina Gisel
Nolly, Mariela
Massarutti, Carolina
Casarini, María Jesús
Garciarena, Carolina Denis
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
author_facet Díaz, Romina Gisel
Nolly, Mariela
Massarutti, Carolina
Casarini, María Jesús
Garciarena, Carolina Denis
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Pérez, Néstor Gustavo
author_sort Díaz, Romina Gisel
title Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
title_short Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
title_full Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
title_fullStr Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
title_full_unstemmed Phosphodiesterase 5A inhibition decreases NHE-1 activity without altering steady state pH<SUB>i</SUB>: Role of phosphatases
title_sort phosphodiesterase 5a inhibition decreases nhe-1 activity without altering steady state ph<sub>i</sub>: role of phosphatases
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/82462
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