Abstract |
Certain forms of cardiac failure appear to be associated with a decrease in the Ca++ sensitivity of the contractile structures, possibly due to troponin I phosphorylation. Interference of cardiotonic drugs with myofibrillar Ca++ activation instead of enhancement of Ca++ influx may therefore provide a more causal therapeutic concept in the treatment of cardiac insufficiency. APP 201-533 (3-Amino-6-methyl-5-phenyl-2(1H)-pyridinone) (the structure of which is shown below) is a novel cardiotonic agent acting neither via beta adrenoceptor stimulation nor inhibition of Na+/K+ ATPase. In the 100 microM concentration range, it increases the Ca++ sensitivity and the Ca++ affinity of functionally isolated cardiac contractile structures. This coincides with an inhibitory effect on the cAMP-dependent protein kinase from rat liver. A possible relation with the regulation of troponin I phosphorylation is discussed.
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Authors | J W Herzig, L H Botelho, R J Solaro |
Journal | Basic research in cardiology
(Basic Res Cardiol)
Vol. 84 Suppl 1
Pg. 117-24
( 1989)
ISSN: 0300-8428 [Print] Germany |
PMID | 2818453
(Publication Type: Journal Article)
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Chemical References |
- Cardiotonic Agents
- Pyridones
- 3-amino-6-methyl-5-phenyl-2(1H)-pyridinone
- Protein Kinases
- Calcium
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Topics |
- Animals
- Calcium
(metabolism)
- Cardiotonic Agents
(pharmacology)
- Dogs
- Heart Failure
(metabolism)
- In Vitro Techniques
- Liver
(enzymology)
- Myocardial Contraction
(drug effects)
- Myofibrils
(metabolism)
- Protein Kinases
(analysis)
- Pyridones
(pharmacology)
- Rats
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