The antiadrenergic effect of neuropeptide Y on the ventricular cardiomyocyte.
The effect of neuropeptide Y (NPY) on adenylate cyclase activity was examined in ventricular myocytes isolated from the adult rat heart. In the presence of the phosphodiesterase inhibitor Ro 20-1724 (0.5 mM) and adenosine deaminase (5 U/ml), these intact cells accumulate cyclic AMP when stimulated by isoproterenol. NPY (10(-9) to 10(-6) M) reduced the degree of cAMP accumulation achieved by 10(-7) M isoproterenol in a dose dependend manner by 10 to maximally 48%. The IC50 value was 3 x 10(-8) M NPY. A maximal concentration (10(-6) M) of N6-phenylisopropyladenosine (PIA) decreased cAMP levels by 39%, i.e. to a similar extent. Prior treatment of the myocytes with pertussis toxin (1 microgram/ml for 6 h) increased the mean stimulated values in the presence of isoproterenol (10(-7) M) by a factor 4.1. In such cells, NPY and PIA were ineffective in antagonizing the stimulation of cAMP production by isoproterenol. These results indicate that the ventricular myocyte has receptors for NPY, similar to the A1 adenosine-receptor in that they are linked to the adenylate cyclase by an inhibitory guanylate binding protein.
Millar
B C
BC
Department of Therapeutics and Pharmacology, Queen's University Belfast, Northern Ireland.
Piper
H M
HM
McDermott
B J
BJ
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D009478:Neuropeptide Y; D010726:Phosphodiesterase Inhibitors; D013565:Sympatholytics; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases