Coupling of adenosine receptors to a pertussis toxin-sensitive G protein in the human heart.
The adenosine receptors in myocardial membranes of human explanted hearts were labeled with the radiolabeled ligand [3H]DPCPX (1,3-dipropyl-8-cyclopentylxanthine). Agonist competition curves revealed high- and low-affinity states. The addition of guanylyl imidodiphosphate (Gpp (NH)p) converted all receptors to a low-affinity state. The portion of high-affinity states and the influence of guanine nucleotides were most pronounced at 22 degrees C. Only low-affinity states could be detected in pertussis toxin-treated membranes. It is concluded that adenosine receptors in the human ventricle couple via a G protein sensitive to pertussis-toxin. Alterations of the coupling of adenosine receptors might have a pathophysiological role in dilated cardiomyopathy in which pertussis toxin substrates are increased.
Böhm
M
M
Medizinische Klinik I der Universität München, F.R.G.
Gierschik
P
P
Ungerer
M
M
Erdmann
E
E
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014970:Xanthines
D006150:Guanine Nucleotides; D011506:Proteins; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D014970:Xanthines; D010660:Phenylisopropyladenosine; D006165:Guanylyl Imidodiphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins