Fasciola hepatica: motility response to metabolic inhibitors in vitro

The effects of metabolic inhibitors on the in vitro motility of Fasciola hepatica have been determined by means of an isometric transducer system. Sodium fluoride, an inhibitor of glycolysis, causes a long-term suppression of motility; this is also the effect of sodium iodoacetate (another glycolysis inhibitor) at low concentrations (1 X 10(-5) M and below). However, higher concentrations of iodoacetate induce a rapid inhibition of activity leading to a spastic paralysis. Both rotenone and oligomycin, which act as inhibitors of oxidative phosphorylation, produce a long-term suppression of movement. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone and carbonylcyanide-m-chlorophenylhydrazone, which are uncouplers of oxidative phosphorylation, induce a spastic paralysis of the fluke; this is rapid at high concentrations (1 X 10(-4) and 1 X 10(-5) M). A brief stimulation of activity is evident at 1 X 10(-5) M and lasts longer at 1 X 10(-6) and 1 X 10(-7) M, before inhibition sets in. There is no stimulation at low concentrations of carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (1 X 10(-8) and 1 X 10(-9) M), only inhibition leading to a medium-term spastic paralysis. In contrast, a third uncoupler, 2,4-dinitrophenol, causes a flaccid paralysis and the effect is rapid only at high concentrations, being accompanied by an initial increase in muscle tone at 1 X 10(-2) M and a brief stimulation of motility at 1 X 10(-3) M. Stimulation lasts longer at 1 X 10(-4) and 1 X 10(-5) M, but is not evident at concentrations below this. The effects on motility at these lower concentrations are essentially long term in nature. That the rapid effects of the uncouplers on muscle tone and motility are not due primarily to uncoupling is shown by 2,4,6-trinitrophenol and hydroquinone, compounds structurally related to 2,4-dinitrophenol. 2,4,6-Trinitrophenol is a membrane-impermeable compound devoid of uncoupling activity; at 1 X 10(-3) M, it causes an immediate inhibition of activity and increase in muscle tone. The antioxidant hydroquinone produces an initial stimulation of motility with some increase in tone, but this is followed by a sharp decline and a short-term flaccid paralysis. The results are discussed in relation to the postulated effects of certain fasciolicides on the energy metabolism of the liver fluke.