Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPYY5 receptors

Neuropeptide Y (NPY) has been shown to participate in the cardiovascular re sponse mediated by the sympathetic system. In this report, we investigate t he growth factor properties of NPY on cardiac myocytes. Mitogen-activated p rotein kinases (MAPK) are key signaling molecules in the transduction of tr ophic signals. Therefore, the role of NPY in inducing MAPK activation was s tudied in mouse neonatal cardiomyocytes, Exposure of neonatal cardiomyocyte s to either NPY, phenylephrine, or angiotensin II induces a rapid phosphory lation of the extracellular responsive kinase, the c-jun N-terminal kinase, and the p38 kinase as well as an activation of protein kinase C (PKC), Mor eover, NPY potentiates phenylephrine-induced MAPK and PKC stimulation. In c ontrast, NPY has no synergistic effect on angiotensin Ii-stimulated MAPK ph osphorylation or PKC activity. NPY effects are pertussis toxin-sensitive an d calcium-independent and are mediated by NPY Y5 receptors. Taken together, these results suggest that NPY, via G(i) protein-coupled NPY Y5 receptors, could participate in the development of cardiac hypertrophy during chronic : sympathetic stimulation by potentiating alpha-adrenergic signals.