Low concentrations of UD-CG 212 enhance myocyte contractility by an increase in calcium responsiveness in the presence of inorganic phosphate

Recent data show that UD-CG 212 in nanomolar concentrations increases myofibrillar Ca++ responsiveness of chemically skinned cardiac preparations in the presence of elevated inorganic phosphate. We studied the effects of UD-CG 212 on cell shortening of intact myocytes and in addition measured the in...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1995-06, Vol.351 (6), p.644-650
Main Authors: van Meel, J C, Redemann, N, Diederen, W, Haigh, R M
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Calcium - metabolism
Cardiotonic Agents - administration & dosage
Cardiotonic Agents - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Fluorescence
Guinea Pigs
In Vitro Techniques
Male
Myocardial Contraction - drug effects
Phosphates - pharmacology
Pyridazines - administration & dosage
Pyridazines - pharmacology
Ventricular Function
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Summary:Recent data show that UD-CG 212 in nanomolar concentrations increases myofibrillar Ca++ responsiveness of chemically skinned cardiac preparations in the presence of elevated inorganic phosphate. We studied the effects of UD-CG 212 on cell shortening of intact myocytes and in addition measured the intracellular calcium transients with the aid of INDO-1 fluorescence in the presence of 5 mM inorganic phosphate. The validity of our experimental system was first tested with the calcium channel opener Bay k 8644. Bay k 8644 at 10(-8) M did not significantly influence myocyte shortening (+ 13.9 +/- 4.6%, n = 9) but at 10(-7) M and 10(-6) M significantly increased contraction by 40.1 +/- 13.6% and 52.5 +/- 17.0% respectively. Bay k 8644 at 10(-8) M increased the INDO-1 fluorescence ratio by 17.3 +/- 4.7% (P < 0.01; n = 9), and at 10(-7) M by 21.5 +/- 4.3% (P < 0.01; n = 9), whereas 10(-6) M Bay k 8644 had no significant effect on peak INDO-1 ratio. However, 10(-7) and 10(-6) M Bay k 8644 accelerated and broadened the calcium transients.
ISSN:0028-1298
1432-1912
DOI:10.1007/BF00170165