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
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.