title: Evidence for adenylate cyclase-coupled A1-adenosine receptors on ventricular cardiomyocytes from adult rat and dog heart.
abstract: Isolated metabolically stable cardiomyocytes from adult rats and mongrel dogs were used to characterize the mechanism underlying the antiadrenergic effect of adenosine. In a system not affected by cellular heterogeneity, isoproterenol (3 x 10(-9) M - 10(-5) M) in the presence of adenosine deaminase (5U/ml) dose dependently increased cellular cAMP (5-80 pmol/mg). The effect of isoproterenol (0.1 microM) was inhibited by various adenosine derivatives, the rank order of potency being in the rat: (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than S-PIA, and in the dog NECA greater than R-PIA greater than S-PIA. The cAMP increase induced by forskolin (1 microM) was attenuated in the rat by R-PIA. 8-phenyltheophylline (3 microM) antagonized the effect of R-PIA on isoproterenol-stimulated cAMP formation. Basal cAMP content was not influenced by R-PIA or NECA. Omission of adenosine deaminase from the incubation medium attenuated the isoproterenol-induced cAMP increase in the rat by about 30%. Our findings provide evidence for the presence of adenylate cyclase-coupled A1-adenosine receptors on cardiomyocytes which may mediate the antiadrenergic effect of adenosine in the heart.
authors.affiliation: Zentrum für Physiologie und Klinische Physiologie, Universität Düsseldorf, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Henrich
authors.forename: H M
authors.initials: HM
authors.lastname: Piper
authors.forename: J
authors.initials: J
authors.lastname: Schrader
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism*
chemical_list: D011983:Receptors, Purinergic; D005576:Colforsin; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000243:Adenosine Deaminase; D000262:Adenylyl Cyclases; D000241:Adenosine; D007545:Isoproterenol