CHARACTERIZATION OF THE ALPHA(1)-ADRENERGIC CHRONOTROPIC RESPONSE IN NEUROPEPTIDE Y-HEATED CARDIOMYOCYTES

The cardiac alpha(1)-adrenergic chronotropic response changes from sti mulatory to inhibitory post-natally. The mature inhibitory response is mediated by the alpha(1B)-adrenoceptor and a pertussis toxin sensitiv e G protein. In vivo and in vitro studies identify sympathetic innerva tion as critical for the maturation of this inhibitory response. Addit ional experiments in a culture model indicate the effect of innervatio n is dependent on neurally released neuropeptide Y. The present study establishes that the individual signaling elements in the neuropeptide Y induced alpha(1)-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 t he putative cardiac Y-3 neuropeptide Y receptor subtype, since it is r eproduced by the peptide fragment neuropeptide Y-(13-36) but not by [L eu(31), Pro(34)]neuropeptide Y. (C) 1998 Elsevier Science B.V. All rig hts reserved.