The effect of diamphenethide on protein synthesis by the liver fluke, Fasciola hepatica.
The effect of the deacetylated (amine) metabolite of diamphenethide (DAMD, 10 micrograms ml-1) on the uptake and incorporation by adult Fasciola hepatica of radioactively labelled precursors of DNA, RNA and protein synthesis ([3H]thymidine, [3H]uridine and [3H]leucine, respectively) was measured by liquid scintillation counting. Comparison was made between the effects of DAMD and those of specific inhibitors of DNA, RNA and protein synthesis, namely, 5-fluorouracil, cordycepin and cycloheximide, respectively. DAMD caused a significant decrease in the overall uptake and incorporation of [3H]uridine by F. hepatica, decreased the incorporation of [3H]leucine and also caused a significant decrease in the overall protein content of the flukes. The effect of DAMD was similar to that of cycloheximide (1 x 10(-3) M), a potent inhibitor of protein synthesis, which also caused a significant decrease in the incorporation of [3H]leucine by the fluke and a decrease in the overall protein content of the fluke. Cordycepin (100 micrograms ml-1) caused a significant decrease in the protein content of the fluke, but had no effect on the uptake or incorporation of [3H]uridine. 5-Fluorouracil (1 x 10(-4) M) did not affect the uptake or incorporation of [3H]thymidine, nor did it decrease the protein content of the fluke. The results indicate that DAMD inhibits protein synthesis by F. hepatica, possibly by inhibiting RNA synthesis. The results are also consistent with previous morphological investigations involving DAMD.
Anderson
H R
HR
School of Biology and Biochemistry, Queen's University of Belfast, Northern Ireland.
Fairweather
I
I
Bamford
D R
DR
Montgomery
W I
WI
D000818:Animals; D002417:Cattle; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D003957:Diamfenetide / Q000494:pharmacology*; D005210:Fasciola hepatica / Q000187:drug effects* / Q000378:metabolism; D015801:Helminth Proteins / Q000096:biosynthesis / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects*; D051381:Rats
D015801:Helminth Proteins; D012313:RNA; D004247:DNA; D003957:Diamfenetide