title: Inhibition of radioligand binding to A1 adenosine receptors by Bay K8644 and nifedipine.
abstract: Two dihydropyridine compounds, Bay K8644 (a calcium entry activator) and nifedipine (a calcium entry blocker), were found to inhibit the binding of [3H]phenylisopropyladenosine ([3H]PIA) to A1 adenosine receptors in rat cerebral cortex membranes with comparable potencies (IC50 10-30 microM). Scatchard analyses indicated that both Bay K8644 and nifedipine inhibited the binding of [3H]PIA by increasing the KD but without significant effect on the Bmax. When tested at 100 microM, neither Bay K8644 nor nifedipine showed a significant effect on [3H]-p-aminoclonidine ([3H]PAC; alpha 2-adrenergic receptor), [3H]dihydroalprenolol ([3H]DHA; beta-adrenergic receptor), [3H]spiperone (dopamine receptor), and [3H]nitrobenzylthioinosine [( 3H]NBMPR; nucleoside transporter) binding. In the presence of 10 mM Mg2+, the ability of 2-chloroadenosine (2-Cl-Ad, an A1 adenosine receptor agonist) to displace [3H]PIA binding was increased. Conversely, the potencies of 1,3-diethyl-8-phenylxanthine (DPX; an A1 receptor antagonist), Bay K8644 and nifedipine in inhibiting [3H]PIA binding were unchanged. It is suggested that both Bay K8644 and nifedipine may act as antagonists of adenosine A1 receptors, in addition to their well-known effects on calcium channels.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010660:Phenylisopropyladenosine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; C027512:1,3-diethyl-8-phenylxanthine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D000241:Adenosine