[3H]nitrendipine-labeled calcium channels discriminate inorganic calcium agonists and antagonists

Abstract

[3H]Nitrendipine binds with high affinity to brain membranes with a drug specificity indicating association with sites mediating the pharmacologic actions of dihydropyridine slow-calcium-channel antagonist drugs. In brain membranes, [3H]nitrendipine binding is absolutely dependent on the presence of calcium ions. Interactions of cation with [3H]nitrendipine binding sites correlate with their physiologic actions at voltage-dependent calcium channels. Ions such as strontium and barium, which mimic calcium physiologically, share the action of calcium in enhancing [3H]nitrendipine binding. Ions such as lanthanum an cobalt, which block the effects of calcium, can inhibit [3H]nitrendipine binding and block the stimulating actions of calcium. The ability to monitor the influence of ions on an agonist-antagonist continuum at [3H]nitrendipine binding sites provides a molecular probe to explore the regulation of cellular function by calcium and other cations.