Intracellular signaling leads to the hypertrophic effect of neuropeptide Y.
Signal transduction pathways involved in the hypertrophic effect of neuropeptide Y (NPY) were investigated in adult cardiomyocytes. Reduction of transforming growth factor-beta activity in serum-supplemented media abolished the induction of hypertrophic responsiveness to NPY. In responsive cells, NPY (100 nM) increased protein synthesis, determined as incorporation of [14C]phenylalanine, by 35 +/- 15% (P < 0.05, n = 16 cultures). In these cells, NPY activated pertussis toxin (PTx)-sensitive G proteins and phosphatidylinositol (PI) 3-kinase. PTx and inhibition of PI 3-kinase abolished the hypertrophic effect of NPY. NPY also activated protein kinase C (PKC) and mitogen-activated protein (MAP) kinase. Inhibition of these two kinases attenuated the induction of creatine kinase (CK)-BB but not the growth response to NPY. In conclusion, NPY stimulates protein synthesis in adult cardiomyocytes via activation of PTx-sensitive G proteins and PI 3-kinase and it induces the fetal-type CK-BB via activation of PKC and MAP kinase.
Goldberg
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Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany.
Taimor
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Piper
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Schlüter
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006332:Cardiomegaly; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D007527:Isoenzymes; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009478:Neuropeptide Y; D010566:Virulence Factors, Bordetella; D007611:Aprotinin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003402:Creatine Kinase; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D020123:Sirolimus; D000077191:Wortmannin