Y. Goldberg et al., INTRACELLULAR SIGNALING LEADS TO THE HYPERTROPHIC EFFECT OF NEUROPEPTIDE-Y, American journal of physiology. Cell physiology, 44(5), 1998, pp. 1207-1215
Signal transduction pathways involved in the hypertrophic effect of ne
uropeptide Y (NPY) were investigated in adult cardiomyocytes. Reductio
n of transforming growth factor-beta activity in serum-supplemented me
dia abolished the induction of hypertrophic responsiveness to NPY. In
responsive cells, NPY (100 nM) increased protein synthesis, determined
as incorporation of [C-14]phenylalanine, by 35 +/- 15% (P < 0.05, n =
16 cultures). In these cells, NPY activated pertussis toxin (PTx)-sen
sitive G proteins and phosphatidylinositol (PI) 3-kinase. PTx and inhi
bition of PI 3-kinase abolished the hypertrophic effect of NPY. NPY al
so 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 conclus
ion, NPY stimulates protein synthesis in adult cardiomyocytes via acti
vation of PTx-sensitive G proteins and PI 3-kinase and it induces the
fetal-type CK-BB via activation of PKC and MAP kinase.