Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart

Previous experiments have shown that acidosis enhances isoproterenol-induced phospholamban (PHL) phosphorylation (Mundina-Weilenmann, C., Vittone, L., Cingolani, H. E., Orchard, C. H. (1996) Am. J. Physiol. 270, C107-C114). In the present experiments, performed in isolated Langendorff perfused rat h...

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Detalles Bibliográficos
Autores principales: Vittone, Leticia Beatriz, Mundiña-Weilenmann, Cecilia, Said, María Matilde, Mattiazzi, Alicia Ramona
Formato: Articulo
Lenguaje:Inglés
Publicado: 1998
Materias:
Ciencias Médicas
Acidosis
Phospholamban phosphorylation
Isoproterenol
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/123077
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-123077
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
Acidosis
Phospholamban phosphorylation
Isoproterenol
spellingShingle Ciencias Médicas
Acidosis
Phospholamban phosphorylation
Isoproterenol
Vittone, Leticia Beatriz
Mundiña-Weilenmann, Cecilia
Said, María Matilde
Mattiazzi, Alicia Ramona
Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
topic_facet Ciencias Médicas
Acidosis
Phospholamban phosphorylation
Isoproterenol
description Previous experiments have shown that acidosis enhances isoproterenol-induced phospholamban (PHL) phosphorylation (Mundina-Weilenmann, C., Vittone, L., Cingolani, H. E., Orchard, C. H. (1996) Am. J. Physiol. 270, C107-C114). In the present experiments, performed in isolated Langendorff perfused rat hearts, phosphorylation site-specific antibodies to PHL combined with the quantitative measurement of 32P incorporation into PHL were used as experimental tools to gain further insight into the mechanism involved in this effect. At all isoproterenol concentrations tested (3-300 nM), phosphorylation of Thr17 of PHL was significantly higher at pHo 6.80 than at pHo 7.40, without significant changes in Ser16 phosphorylation. This increase in Thr17 phosphorylation was associated with an enhancement of the isoproterenol-induced relaxant effect. In the absence of isoproterenol, the increase in [Ca]o at pHo 6.80 (but not at pHo 7.40) evoked an increase in PHL phosphorylation that was exclusively due to an increase in Thr17 phosphorylation and that was also associated with a significant relaxant effect. This effect and the phosphorylation of Thr17 evoked by acidosis were both offset by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62. In the presence of isoproterenol, either the increase in [Ca]o or the addition of a 1 microM concentration of the phosphatase inhibitor okadaic acid was able to mimic the increase in isoproterenol-induced Thr17 phosphorylation produced by acidosis. In contrast, these two interventions have opposite effects on phosphorylation of Ser16. Whereas the increase in [Ca]o significantly decreased phosphorylation of Ser16, the addition of okadaic acid significantly increased the phosphorylation of this residue. The results are consistent with the hypothesis that the increase in phospholamban phosphorylation produced by acidosis in the presence of isoproterenol is the consequence of two different mechanisms triggered by acidosis: an increase in [Ca2+]i and an inhibition of phosphatases.
format Articulo
Articulo
author Vittone, Leticia Beatriz
Mundiña-Weilenmann, Cecilia
Said, María Matilde
Mattiazzi, Alicia Ramona
author_facet Vittone, Leticia Beatriz
Mundiña-Weilenmann, Cecilia
Said, María Matilde
Mattiazzi, Alicia Ramona
author_sort Vittone, Leticia Beatriz
title Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
title_short Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
title_full Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
title_fullStr Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
title_full_unstemmed Mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
title_sort mechanisms involved in the acidosis enhancement of the isoproterenol-induced phosphorylation of phospholamban in the intact heart
publishDate 1998
url http://sedici.unlp.edu.ar/handle/10915/123077
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