The negative inotropic effect of neuropeptide Y on the ventricular cardiomyocyte.
The effect of neuropeptide Y (NPY) on cell contractions of ventricular myocytes isolated from the adult rat heart was investigated. Maximum changes in cell length (dL) during stimulated (0.5 Hz) contractions were determined in presence of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) and adenosine deaminase (5 U/ml). Under these basal conditions NPY (10(-6) M) reduced dL by 39% of control. Isoproterenol (10(-6) M) increased dL by 105% of control; the EC50 was 2 x 10(-9) M. NPY reduced the increase in dL achieved by isoproterenol in a dose dependent manner. The IC50 value was 1 x 10(-9) M and NPY (10(-6) M) produced complete inhibition. In the absence of the phosphodiesterase inhibitor the IC50 was 4 x 10(-9) M. The EC50 of isoproterenol and IC50 of NPY producing accumulation of cAMP in myocytes (Millar et al. 1988) exceeded the respective values of dL by one order of magnitude. Prior treatment of the myocytes with pertussis toxin abolished the potency of NPY to antagonize the increase in dL by isoproterenol while not interfering with the response to the beta-agonist. These results demonstrate a negative inotropic effect of NPY on the ventricular myocardial cell. Complete abolition of the effect of NPY by pertussis toxin indicate that this effect is mediated by a sarcolemmal receptor for NPY linked to adenylate cyclase via an inhibitory guanine nucleotide binding protein.
Piper
H M
HM
Physiologisches Institut I, Universität Düsseldorf, Federal Republic of Germany.
Millar
B C
BC
McDermott
B J
BJ
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D009478:Neuropeptide Y / Q000494:pharmacology*; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D009478:Neuropeptide Y; D010726:Phosphodiesterase Inhibitors; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol