Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulin
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...
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| Published in | Biochemical and biophysical research communications Vol. 105; no. 3; pp. 1142 - 1149 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.01.1982
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| Subjects | |
| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | The calcium antagonists, nimodipine and nicardipine, competitively inhibited calmodulin-sensitive and calmodulin-insensitive forms of cyclic AMP phosphodiesterase, with IC sub(50's) in 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. 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. The calcium antagonists, nimodipine and nicardipine, competitively inhibited calmodulin-sensitive and calmodulin-insensitive forms of cyclic AMP phosphodiesterase, with IC sub(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 against calmodulin-sensitive forms of the enzyme. Verapamil and nimodipine both antagonized the calmodulin stimulation of phosphodiesterase. |
| Author | Hachisu, Reiko Epstein, Paul M. Andrenyak, David M. Fiss, Karen |
| Author_xml | – sequence: 1 givenname: Paul M. surname: Epstein fullname: Epstein, Paul M. – sequence: 2 givenname: Karen surname: Fiss fullname: Fiss, Karen – sequence: 3 givenname: Reiko surname: Hachisu fullname: Hachisu, Reiko – sequence: 4 givenname: David M. surname: Andrenyak fullname: Andrenyak, David M. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/6284165$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | 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 |
| Title | Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulin |
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