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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-9-16
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pubmed:abstractText |
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 ?mol/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 ?mol/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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/Dicarboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase 5 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protons,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 90-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/endothall,
http://linkedlifedata.com/resource/pubmed/chemical/sildenafil
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1524-4563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
690-5
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20713918-Animals,
pubmed-meshheading:20713918-Biological Transport,
pubmed-meshheading:20713918-Cats,
pubmed-meshheading:20713918-Cells, Cultured,
pubmed-meshheading:20713918-Cyclic Nucleotide Phosphodiesterases, Type 5,
pubmed-meshheading:20713918-Dicarboxylic Acids,
pubmed-meshheading:20713918-Enzyme Inhibitors,
pubmed-meshheading:20713918-Hydrogen-Ion Concentration,
pubmed-meshheading:20713918-Immunoblotting,
pubmed-meshheading:20713918-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:20713918-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:20713918-Myocytes, Cardiac,
pubmed-meshheading:20713918-Okadaic Acid,
pubmed-meshheading:20713918-Phosphodiesterase 5 Inhibitors,
pubmed-meshheading:20713918-Phosphodiesterase Inhibitors,
pubmed-meshheading:20713918-Phosphorylation,
pubmed-meshheading:20713918-Piperazines,
pubmed-meshheading:20713918-Protein Phosphatase 1,
pubmed-meshheading:20713918-Protons,
pubmed-meshheading:20713918-Purines,
pubmed-meshheading:20713918-Ribosomal Protein S6 Kinases, 90-kDa,
pubmed-meshheading:20713918-Sodium-Hydrogen Antiporter,
pubmed-meshheading:20713918-Sulfones
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pubmed:year |
2010
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pubmed:articleTitle |
Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity.
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pubmed:affiliation |
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP, La Plata, Argentina.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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