On the cardiac contractile, electrophysiological and biochemical effects of endothall, a protein phosphatase inhibitor

Citation
P. Boknik et al., On the cardiac contractile, electrophysiological and biochemical effects of endothall, a protein phosphatase inhibitor, PHARMACOL, 61(1), 2000, pp. 43-50
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGY
ISSN journal
0031-7012 → ACNP
Volume
61
Issue
1
Year of publication
2000
Pages
43 - 50
Database
ISI
SICI code
0031-7012(2000)61:1<43:OTCCEA>2.0.ZU;2-P
Abstract
Protein phosphatase inhibitors, e.g. cantharidin, exert positive inotropic effects in mammalian heart preparations. Endothall, a synthetic herbicide w hich is chemically related to cantharidin, inhibits protein phosphatase act ivities in mouse liver preparations. However, the cardiac effects of endoth all have hitherto not been studied. in guinea pig papillary muscles, endoth all (1-100 mu mol/l) failed to affect force of contraction, whereas canthar idin (1-100 mu mol/l) increased force of contraction maximally to 313.4 +/- 32% of control at 10 mu mol/l. In isolated guinea pig ventricular cardiomy ocytes, endothall did neither change the free intracellular calcium concent ration nor the amplitude of calcium current nor the phosphorylation state o f regulatory phosphoproteins like phospholamban. In contrast, cantharidin ( 30 mu mol/l) increased the free intracellular calcium concentration and the L-type calcium current to 149.6 +/- 9% and to 157.6 +/- 12% of control, re spectively. Furthermore, cantharidin (1-100 mu mol/l) augmented the phospho rylation of phospholamban maximally to 140.8 +/- 7% of control. Nevertheles s, in guinea pig ventricular homogenates, both endothall and cantharidin in hibited phosphatase activity with EC50 values of 1.92 and 0.32 mu mol/l, re spectively. Thus, in contrast to cantharidin, endothall failed to increase force of contraction, though it inhibited protein phosphatase activity. Cle arly, endothall is not an appropriate tool to study the function of protein phosphatases in the mammalian heart. Copyright (C) 2000 S. Karger AG, Base l.