The effects of isoliquiritigenin on force of contraction (F-c), L-type
Ca2+ current (I-CA) and intracellular Ca2+ concentration ([Ca2+](i))
were investigated in rat ventricular heart muscle. Isoliquiritigenin i
ncreased F-c and I-Ca and, after longer exposure times, resting tensio
n and [Ca2+](i). The effect of isoliquiritigenin (100 mu M) on I-Ca wa
s diminished by Rp-cAMPS (30 mu M). 1H-[1,2,4]oxa-diazolo[4,3-a]quinox
alin-1-one (50 mu M) did not influence the effects of isoliquiritigeni
n on F-c and I-Ca. The positive inotropic effects of isoprenaline and
forskolin, but not of 3-isobutyl-1-methylxanthine, were potentiated by
isoliquiritigenin (100 mu M). In the presence of milrinone (10 mu M),
no further effects of isoliquiritigenin (100 mu M) on F-c and I-Ca we
re observed. It is suggested that the increase in F-c and I-Ca by isol
iquiritigenin is due to an accumulation of cyclic AMP. These effects a
re probably unrelated to an effect of the drug on soluble guanylyl cyc
lase, as reported for smooth muscle, but rather due to a direct inhibi
tion of phosphodiesterase III activity.