Characterization of the alpha1-adrenergic chronotropic response in neuropeptide Y-treated cardiomyocytes.
The cardiac alpha1-adrenergic chronotropic response changes from stimulatory to inhibitory post-natally. The mature inhibitory response is mediated by the alpha1B-adrenoceptor and a pertussis toxin sensitive G protein. In vivo and in vitro studies identify sympathetic innervation as critical for the maturation of this inhibitory response. Additional experiments in a culture model indicate the effect of innervation is dependent on neurally released neuropeptide Y. The present study establishes that the individual signaling elements in the neuropeptide Y induced alpha1-adrenergic cascade are the same as those appearing during normal in vivo development. In addition, the data demonstrate that the effect of neuropeptide Y does not result from activation of the putative cardiac Y3 neuropeptide Y receptor subtype, since it is reproduced by the peptide fragment neuropeptide Y-(13-36) but not by [Leu31, Pro34]neuropeptide Y.
Department of Anesthesiology, Columbia University, New York, NY 10032, USA.
L S
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Sun
V O
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Rybin
S F
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Steinberg
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Robinson
D000818:Animals; D000833:Animals, Suckling; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology*; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009478:Neuropeptide Y; D018340:Receptors, Adrenergic, alpha-1; D017476:Receptors, Neuropeptide Y; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins