Intracellular signaling leads to the hypertrophic effect of neuropeptide Y

Signal transduction pathways involved in the hypertrophic effectof neuropeptide Y (NPY) were investigated in adult cardiomyocytes. Reduction of transforming growth factor- activity inserum-supplemented media abolished the induction of hypertrophicresponsiveness to NPY. In responsive cells, NPY (100 nM) increasedprotein synthesis, determined as incorporation of¹⁴C]phenylalanine, by35 ± 15% (P < 0.05, n = 16 cultures). In these cells, NPYactivated pertussis toxin (PTx)-sensitive G proteins andphosphatidylinositol (PI) 3-kinase. PTx and inhibition of PI 3-kinaseabolished the hypertrophic effect of NPY. NPY also activated proteinkinase C (PKC) and mitogen-activated protein (MAP) kinase. Inhibitionof these two kinases attenuated the induction of creatine kinase(CK)-BB but not the growth response to NPY. In conclusion, NPYstimulates protein synthesis in adult cardiomyocytes via activation ofPTx-sensitive G proteins and PI 3-kinase and it induces the fetal-typeCK-BB via activation of PKC and MAP kinase.