Pharmacology
Original Paper
On the Cardiac Contractile, Electrophysiological and Biochemical Effects of Endothall, a Protein Phosphatase InhibitorBokník P. · Vahlensieck U. · Huke S. · Knapp J. · Linck B. · Lüss H. · Müller F.U. · Neumann J. · Schmitz W.Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Deutschland
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Article / Publication Details
Published online: July 07, 2000
Issue release date: July 2000
Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
Abstract
Protein phosphatase inhibitors, e.g. cantharidin, exert positive inotropic effects in mammalian heart preparations. Endothall, a synthetic herbicide which is chemically related to cantharidin, inhibits protein phosphatase activities in mouse liver preparations. However, the cardiac effects of endothall have hitherto not been studied. In guinea pig papillary muscles, endothall (1–100 μmol/l) failed to affect force of contraction, whereas cantharidin (1–100 μmol/l) increased force of contraction maximally to 313.4 ± 32% of control at 10 μmol/l. In isolated guinea pig ventricular cardiomyocytes, endothall did neither change the free intracellular calcium concentration nor the amplitude of calcium current nor the phosphorylation state of regulatory phosphoproteins like phospholamban. In contrast, cantharidin (30 μmol/l) increased the free intracellular calcium concentration and the L-type calcium current to 149.6 ± 9% and to 157.6 ± 12% of control, respectively. Furthermore, cantharidin (1–100 μmol/l) augmented the phosphorylation of phospholamban maximally to 140.8 ± 7% of control. Nevertheless, in guinea pig ventricular homogenates, both endothall and cantharidin inhibited phosphatase activity with EC50 values of 1.92 and 0.32 μmol/l, respectively. Thus, in contrast to cantharidin, endothall failed to increase force of contraction, though it inhibited protein phosphatase activity. Clearly, endothall is not an appropriate tool to study the function of protein phosphatases in the mammalian heart.
© 2000 S. Karger AG, Basel
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Article / Publication Details
Published online: July 07, 2000
Issue release date: July 2000
Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
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