Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1992-2-18
|
| pubmed:abstractText |
Pimobendan (UD-CG 115 BS), an inotropic agent and inhibitor of type III phosphodiesterase activity, is demethylated in vivo to form UD-CG 212 Cl, which is a more potent type III phosphodiesterase inhibitor. This study examined cyclic AMP (cAMP)-mediated actions of UD-CG 212 Cl. In guinea pig papillary muscles, UD-CG 212 Cl increased cAMP and stimulated Ca(++)-dependent slow action potentials (APs) in a dose-dependent manner. When compared to previous studies using pimobendan, UD-CG 212 Cl was approximately 100-fold more potent. UD-CG 212 Cl had no additional effects on slow APs in the presence of a maximal dose of isoproterenol (1 microM). Propranolol had little effect on UD-CG 212 Cl-induced slow APs. These results, along with previous studies, indicate that slow AP induction by UD-CG 212 Cl was cAMP-dependent, and the increase in cAMP levels was most likely due to phosphodiesterase inhibition and not beta receptor stimulation. Experiments with tetraethylammonium.Cl suggested that UD-CG 212 Cl probably did not induce slow APs by blocking K+ channels. In voltage-clamped ventricular myocytes UD-CG 212 Cl (100 microM) could stimulate Ca++ current (+21 +/- 5%) when basal cAMP levels were enhanced with a submaximal dose of isoproterenol (10(-9)-10(-8) M). Isoproterenol was not required to observe the stimulating effect of UD-CG 212 Cl on Ca++ current in intact, nondialyzed cells prepared using the nystatin-perforated patch method. Studies with the stereoisomers of UD-CG 212 Cl showed that the D-isomer was more potent than the L-isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cardiotonic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridazines,
http://linkedlifedata.com/resource/pubmed/chemical/Tetraethylammonium,
http://linkedlifedata.com/resource/pubmed/chemical/Tetraethylammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/UD CG 212 Cl
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
260
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
58-63
|
| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:1346167-Action Potentials,
pubmed-meshheading:1346167-Adrenergic beta-Agonists,
pubmed-meshheading:1346167-Adrenergic beta-Antagonists,
pubmed-meshheading:1346167-Animals,
pubmed-meshheading:1346167-Calcium,
pubmed-meshheading:1346167-Cardiotonic Agents,
pubmed-meshheading:1346167-Cells, Cultured,
pubmed-meshheading:1346167-Cyclic AMP,
pubmed-meshheading:1346167-Electrophysiology,
pubmed-meshheading:1346167-Guinea Pigs,
pubmed-meshheading:1346167-Heart,
pubmed-meshheading:1346167-Heart Ventricles,
pubmed-meshheading:1346167-Myocardial Contraction,
pubmed-meshheading:1346167-Myocardium,
pubmed-meshheading:1346167-Papillary Muscles,
pubmed-meshheading:1346167-Phosphodiesterase Inhibitors,
pubmed-meshheading:1346167-Pyridazines,
pubmed-meshheading:1346167-Stereoisomerism,
pubmed-meshheading:1346167-Tetraethylammonium,
pubmed-meshheading:1346167-Tetraethylammonium Compounds,
pubmed-meshheading:1346167-Ventricular Function
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| pubmed:year |
1992
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| pubmed:articleTitle |
Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in guinea pig myocardium.
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| pubmed:affiliation |
Department of Physiology and Biophysics, University of Illinois, Chicago.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.
|