title: Neuropeptide Y modifies the hypertrophic response of adult ventricular cardiomyocytes to norepinephrine.
abstract: OBJECTIVE
  The hypertrophic response of adult rat cardiomyocytes to norepinephrine via alpha-adrenoceptor stimulation is limited by an inhibitory cross-talk of simultaneously beta-adrenoceptor stimulation. On the other hand, neuropeptide Y (NPY), known to be co-secreted with norepinephrine from intramural nerve endings of the heart, exerts an anti-beta-adrenergic effect. Therefore, it should be expected that NPY enhances the hypertrophic response to norepinephrine. This hypothesis was addressed in the present study.
  
  
  METHODS
  Isolated adult ventricular cardiomyocytes from rats were used. As parameters of hypertrophic growth we investigated cell volume, cross-sectional area, protein mass. Protein and RNA synthesis were determined by incorporation of [(14)C]phenylalanine or [(14)C]uridine, respectively.
  
  
  RESULTS
  Norepinephrine (1 micromol/l) did not significantly increase protein or RNA synthesis. In co-presence of NPY (100 nmol/l), however, norepinephrine increased protein synthesis by 44% and RNA synthesis by 18%. Under the same conditions, NPY enhanced the effect of norepinephrine on cell volume from +6.4 to +18.2%, its effect on cross-sectional area from +16 to +23%, and increased the protein/DNA ratio from 32.5 to 35.6 mg/mg. In parallel, norepinephrine caused a translocation of PKC-alpha and PKC-delta into the particular fractions and this effect of norepinephrine was also enhanced by co-presence of NPY. In contrast, NPY did not enhance ERK-activation caused by norepinephrine.
  
  
  CONCLUSIONS
  Our study indicates the anti-beta-adrenergic effect of NPY is sufficient to modulate the hypertrophic response of adult ventricular cardiomyocytes to norepinephrine. The results suggest that the hypertrophic effect of norepinephrine via alpha-adrenoceptor stimulation can be modulated by co-release of NPY from intramural nerve endings.
authors.affiliation: Physiologisches Institut, Justus-Liebig-Universität Giessen, Aulweg 129, D-35392 Giessen, Germany.
authors.forename: Marat
authors.initials: M
authors.lastname: Kanevskij
authors.forename: Gerhild
authors.initials: G
authors.lastname: Taimor
authors.forename: Matthias
authors.initials: M
authors.lastname: Schäfer
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Piper
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schlüter
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010649:Phenylalanine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D015398:Signal Transduction; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D009478:Neuropeptide Y; D018342:Receptors, Adrenergic, beta-1; D010649:Phenylalanine; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D009638:Norepinephrine