The in vitro secretion of acetylcholinesterase by adult stages of Heligmosomoides polygyrus: the effects of broad-spectrum anthelmintics

The secretion of acetylcholinesterase (AChE) by female and male Heligmosomo ides polygyrus was studied in different in vitro culture media. AChE secret ion was increased in the presence of fetal calf serum or bovine serum album in (BSA). In the absence of crowding effects, specific AChE activity in exc retion/secretion products was higher for male (2.41 +/- 0.07 mu mol min(-1) mg(-1)) than for female (0.56 +/- 0.04 mu mol min(-1)mg(-1)) worms but on a per nematode basis both sexes showed comparable rates of secretion. Acety lthiocholine iodide was the favoured substrate of the enzyme. When the nema todes were incubated in vitro with albendazole (ABZ), ricobendazole (RBZ), mebendazole (MBZ), levamisole (LVM), morantel (MRT) or ivermectin (IVM), at concentrations from 1 mM to 10 nM, in RPMI medium for 2 or 6 h and then tr ansferred to a drug-free medium (RPMI medium supplemented with 0.5% BSA) fo r 24h or continuously exposed to the drugs in supplement-free medium (24h), the concentrarion- and time-dependent inhibitory: effects on AChE secretio n mere observed. The continued exposure to the drugs for all incubation per iods (with a single exception for LVM 1 nM) produced the highest levels of inhibition. Under these conditions, the concentrations inhibiting the secre tion of AChE by 50% (IC50) relative to drug-free controls were estimated. T he IC50 values ranged from 0.012 mu M (IVM) to 2.96 mu M (MRT). The potenti al of this bioassay for the selective primary evaluation of new compounds w ith broad-spectrum anti-nematodal activity is discussed.