The signal transduction pathway causing the synergistic hypertrophic effects of neuropeptide Y and norepinephrine on primary cardiomyocyte.
To investigate the synergistic hypertrophic effects of neuropeptide Y (NPY) and norepinephrine (NE) and its possible signal transduction pathway on primary cardiomyocytes, neonatal cardiomyocytes were exposed to NPY, NE or angiotensin II (AnII). All three agonists induced hypertrophic effects, stimulated protein kinase C (PKC) and activated mitogen-activated protein kinase (MAPK). Moreover, NPY at sub-optimal concentration potentiated NE-, not AnII-, induced all of the above effects. Pretreatment with phorbol 12-myristate 13-acetate (PMA) completely abolished these effects for both NE and NPY. NPY potentiation was calcium-independent and pertussis toxin (PTX)-sensitive, and was different from NPY direct hypertrophic effect on cardiomyocyte, as PTX only partially abolished NPY-induced hypertrophic effects. Taken together, NPY participated in the development of cardiac hypertrophy by potentiating NE effects. The signal pathway involves PTX-sensitive G protein, PKC, MAPK, and does not require the presence of calcium.
Zeng
C
C
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China. cyzeng1@hotmail.com
Zhou
Y
Y
Liu
G
G
Sun
W
W
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006984:Hypertrophy / Q000503:physiopathology*; D007930:Leucine / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019284:Thapsigargin; D037342:Pertussis Toxin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D007930:Leucine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine