Summary
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 EC 50 was 2 x 10−9 M. NPY reduced the increase in dL achieved by isoproterenol in a dose dependent manner. The IC 50 value was 1 × 10−9 M and NPY (10−6 M) produced complete inhibition. In the absence of the phosphodiesterase inhibitor the IC50 was 4 × 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 β-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.
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Abbreviations
- NPY:
-
neuropeptide Y
- PIA:
-
(−)-N6-phenyliso-propyl-adenosine
- Ro 20-1724:
-
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone
- Hepes:
-
4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid
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Michael Piper, H., Cherie Millar, B. & McDermott, B.J. The negative inotropic effect of neuropeptide Y on the ventricular cardiomyocyte. Naunyn-Schmiedeberg's Arch Pharmacol 340, 333–337 (1989). https://doi.org/10.1007/BF00168519
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DOI: https://doi.org/10.1007/BF00168519