Pertussis toxin unmasks stimulatory myocardial A2-adenosine receptors on ventricular cardiomyocytes.
Pertussis toxin-pretreatment abolished the contractility- and cAMP-decreasing effects of the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (R-PIA) in the presence of isoprenaline in isolated ventricular cardiomyocytes from guinea-pigs, indicating that these stimulatory effects of A1-adenosine receptors are mediated via pertussis toxin-sensitive G-proteins. Furthermore, the decrease in contractile response by the A1/A2-adenosine receptor agonist 5'-N-ethylcarboxamidadenosine (NECA) was abolished. Moreover, NECA increased cAMP content in pertussis toxin-pretreated cells. Thus, pertussis toxin unmasked cAMP-augmenting effects of NECA, indicating that NECA can stimulate A2-adenosine receptors on cardiomyocytes. Thereby, the present study provides evidence that besides cAMP- and contractility-decreasing A1-adenosine receptors, cAMP-increasing A2-adenosine receptors coexist on ventricular cardiomyocytes, which do not influence contractile response.
Stein
B
B
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Mende
U
U
Neumann
J
J
Schmitz
W
W
Scholz
H
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D007545:Isoproterenol