Effect of dynorphin A(1-13) on cardiomyocytes in culture: modulation of the response to increased extracellular calcium, but no effect on intrinsic cardiac contractile frequency or the response to isoproterenol or increased extracellular potassium.
The purpose of this study was to determine whether the endogenous opioid peptide dynorphin A(1-13) has a direct effect on the heart or acts to modulate the cardiac chronotropic response to calcium, potassium, or beta-adrenergic receptor stimulation. Spontaneously contracting myocardial cell aggregates were prepared from 7-day-old chick embryos and were maintained in culture for 72 h before study. Dynorphin A(1-13), 10(-8) to 10(-6)M, did not alter spontaneous contractile frequency. Increases in [Ca2+]o spontaneously suppressed cardiac contractile frequency, and dynorphin A(1-13) significantly (p less than 0.05) enhanced this response. Nifedipine, 10(-8) M, antagonized the effect of increased [Ca2+]o on cardiac contractile frequency, but did not block the action of dynorphin A(1-13) to accentuate the effect of increasing [Ca2+]o. Dynorphin A(1-13) did not alter the significant (p less than 0.05) increase in contractile frequency produced by beta-adrenergic receptor stimulation by isoproterenol, or the suppression in contractile frequency produced by increases in extracellular potassium ([K+]o). These data indicate that dynorphin A(1-13) does not act directly on the cardiac myocyte to alter cardiac contractile frequency or alter the response to increases in [K+]o or to isoproterenol, but that dynorphin A(1-13) does modulate the response to increases in extracellular calcium.
University Hospital (Shaughnessy), University of British Columbia, Vancouver, Canada.
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Rabkin
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology*; D007545:Isoproterenol; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D009543:Nifedipine; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium
D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins; D009543:Nifedipine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium