1. Duality of G protein-coupled mechanisms for β-adrenergic activation of NKCC activity in skeletal muscle
- Author
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Jennifer A. Wong, Aidar R. Gosmanov, and Donald B. Thomason
- Subjects
MAPK/ERK pathway ,medicine.medical_specialty ,Sodium-Potassium-Chloride Symporters ,Physiology ,G protein ,8-Bromo Cyclic Adenosine Monophosphate ,Enzyme Activators ,GTP-Binding Protein alpha Subunits, Gi-Go ,In Vitro Techniques ,Protein Serine-Threonine Kinases ,Pertussis toxin ,medicine.disease_cause ,chemistry.chemical_compound ,GTP-Binding Proteins ,Proto-Oncogene Proteins ,Internal medicine ,Receptors, Adrenergic, beta ,GTP-Binding Protein alpha Subunits, Gs ,medicine ,Animals ,Virulence Factors, Bordetella ,Phosphorylation ,Muscle, Skeletal ,Protein kinase A ,Mitogen-Activated Protein Kinase 1 ,Soleus muscle ,Mitogen-Activated Protein Kinase 3 ,Forskolin ,Chemistry ,Cholera toxin ,Skeletal muscle ,Cell Biology ,Adrenergic beta-Agonists ,Cyclic AMP-Dependent Protein Kinases ,Rats ,Enzyme Activation ,Proto-Oncogene Proteins c-raf ,Endocrinology ,medicine.anatomical_structure ,Pertussis Toxin ,Female ,Mitogen-Activated Protein Kinases ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Skeletal muscle Na+-K+-2Cl−cotransporter (NKCC) activity provides a potential mechanism for regulated K+uptake. β-Adrenergic receptor (β-AR) activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent manner. We examined potential G protein-coupled pathways for β-AR-stimulated NKCC activity. Inhibition of Gs-coupled PKA blocked isoproterenol-stimulated NKCC activity in both the slow-twitch soleus muscle and the fast-twitch plantaris muscle. However, the PKA-activating agents cholera toxin, forskolin, and 8-bromo-cAMP (8-BrcAMP) were not sufficient to activate NKCC in the plantaris and partially stimulated NKCC activity in the soleus. Isoproterenol-stimulated NKCC activity in the soleus was abolished by pretreatment with pertussis toxin (PTX), indicating a Gi-coupled mechanism. PTX did not affect the 8-BrcAMP-stimulated NKCC activity. PTX treatment also precluded the isoproterenol-mediated ERK1/2 MAPK phosphorylation in the soleus, consistent with NKCC's MAPK dependency. Inhibition of isoproterenol-stimulated ERK activity by PTX treatment was associated with an increase in Akt activation and phosphorylation of Raf-1 on the inhibitory residue Ser259. These results demonstrate a novel, muscle phenotype-dependent mechanism for β-AR-mediated NKCC activation that involves both Gsand Giprotein-coupled mechanisms.
- Published
- 2002