Inhibition of radioligand binding to A1 adenosine receptors by Bay K8644 and nifedipine.

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.