Specific binding of a calcium channel activator, [ 3H]BAY k 8644, to membranes from cardiac muscle and brain

• Published in: Biochemical and biophysical research communications Vol. 121; no. 1; pp. 317 - 323
• Main Authors: Janis, R.A., Rampe, D., Sarmiento, J.G., Triggle, D.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.1984
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Binding Sites; Binding, Competitive; Brain - metabolism; Calcium - metabolism; Cell Membrane - metabolism; Female; Guinea Pigs; In Vitro Techniques; Ion Channels - drug effects; Myocardium - metabolism; Nifedipine - analogs & derivatives; Nifedipine - metabolism; Nitrendipine; Rabbits
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(84)90725-3

BAY k 8644 is a member of a new class of drugs that directly activates Ca 2+ channels. This 1,4-dihydropyridine was found to bind to both high and low affinity sites on rabbit ventricular microsomes and guinea pig brain synaptosomes. The dissociation constant obtained from Scatchard analysis with [ 3H]BAY k 8644 was 2 to 3 nM for the high affinity binding site, and the estimated maximal number of binding sites was 0.8 and 0.4 pmol/mg protein for heart and brain membranes, respectively, at 15°C. Competition between nitrendipine and [ 3H]BAY k 8644 indicated a common high affinity binding site for Ca 2+ channel activators and antagonists. The results suggest that the 1,4-dihydropyridine Ca 2+ channel antagonists do not act as simple channel plugs.