Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulin

• Published in: Biochemical and biophysical research communications Vol. 105; no. 3; pp. 1142 - 1149
• Main Authors: Epstein, Paul M., Fiss, Karen, Hachisu, Reiko, Andrenyak, David M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.1982
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - metabolism; 3':5'-cyclic-nucleotide phosphodiesterase; Animals; Brain - enzymology; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Calcium-Binding Proteins - metabolism; calmodulin; Calmodulin - metabolism; Chickens; Cytosol - enzymology; Dogs; Humans; Kidney - enzymology; Kinetics; Lymphocytes - enzymology; Myocardium - enzymology; Nicardipine; Nicotinic Acids - pharmacology; Nifedipine - analogs & derivatives; Nifedipine - pharmacology; Nimodipine; proadifen; Pyridines - pharmacology; Rats; Spectrometry, Fluorescence; verapamil
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(82)91089-0

The calcium antagonists, nimodipine and nicardipine, competitively inhibited calmodulin-sensitive and calmodulin-insensitive forms of cyclic AMP phosphodiesterase, with IC 50's in the micromolar range. Verapamil showed similar inhibitory potency against calmodulin-insensitive phosphodiesterases, but in marked contrast, it was a very weak inhibitor (30–100 times less potent) against calmodulin-sensitive forms of the enzyme. Verapamil and nimodipine both antagonized the calmodulin stimulation of phosphodiesterase. Through use of hydrophobic fluorescent probes, verapamil, and another calmodulin antagonist, proadifen, were shown to interact directly with calmodulin in a manner that differed from the interaction of calmodulin with trifluoperazine.