[3H]Nitrendipine-Labeled Calcium Channels Discriminate Inorganic Calcium Agonists and Antagonists

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 79; no. 11; pp. 3656 - 3660
• Main Authors: Gould, Robert J., Kenneth M. M. Murphy, Snyder, Solomon H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.06.1982; National Acad Sciences
• Subjects: Agonists; Animals; Binding sites; Brain - metabolism; Brain Mapping; Calcium; Calcium - antagonists & inhibitors; Calcium - metabolism; Calcium channels; Cations, Divalent - metabolism; Cobalt; Dihydropyridines; Guinea Pigs; Ion Channels - drug effects; Ion Channels - metabolism; Ions; Kinetics; Lanthanum; Male; Manganese; Nifedipine - analogs & derivatives; Nifedipine - metabolism; Nitrendipine; Pyridines - metabolism; Rats; Strontium; Tissue Distribution
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.11.3656

[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 cations 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 and 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.