Activation of Na+/Ca2+ exchange by adenosine in ewe heart sarcolemma is mediated by a pertussis toxin-sensitive G protein.
We studied the effect of adenosine on Na+/Ca2+ exchange activity in ewe heart ventricular sarcolemmal vesicles. Adenosine was found to stimulate Na+/Ca2+ exchange activity in a dose-dependent manner from 0.1 nM to 10 microM, with maximal stimulation (40%) at 0.1 microM adenosine. The Vmax of Na+/Ca2+ exchange was increased, but the Km for Ca2+ was not altered. The effect of adenosine was specific since 1 microM adenine, inosine, and guanosine led to less than 15% stimulation, and adenosine diphosphate had no effect. Caffeine antagonized the activation of Na+/Ca2+ exchange by adenosine, and the order of potency of adenosine analogs was N6-(L-2-phenylisopropyl)adenosine = N6-cyclohexyladenosine = 5'-(N- ethylcarboxamido)adenosine much greater than N6-(D-2-phenylisopropyl)adenosine, indicating the involvement of A1 subclass receptors. The effect of adenosine was mimicked by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and blocked by pertussis toxin treatment. Taken together, these results suggest that A1 subclass receptors coupled to a pertussis toxin-sensitive G protein mediate the activation of Na+/Ca2+ exchange activity by adenosine. We conclude that the negative inotropic effect of adenosine in ventricular muscle, antagonistic toward cyclic AMP, may involve activation of Na+/Ca2+ exchange.
Brechler
V
V
Institut National de la Santé et de la Recherche Médicale, Hôpital Henri Mondor, Créteil, France.
Pavoine
C
C
Lotersztajn
S
S
Garbarz
E
E
Pecker
F
F
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism; D007288:Inosine / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D012964:Sodium / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D006151:Guanosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D007288:Inosine; D012964:Sodium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D002118:Calcium