Ref ID : 7249
Robin A. Woods, Kathleen M.B. Malone, Cheryl A. Albuquerque, and George Tomlinson; The effects of amidantel (BAY d 8815) and it deacylated derivative (BAY d 9216) on wild-type and resistant mutants of Caenorhabditis elegans. Can.J.Zool. 64:1310-1316, 1986
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The anthelmintic drugs amidantel (BAY d 8815) and its deacylated derivative (BAY d 9216) inhibited the growth of wild-type (N2) Caenorhabditis elegans but had little effect on development or reproductive capacity. Inhibition of growth correlated well with drug-induced paralysis, both becoming maximal at around 1.0 mM concentration of either drug. Egg laying was delayed by about 24 hr and the rate of laying was only about 60-70% of the controls. However, the period during which eggs were laid was extended by a similar amount and the total number of eggs laid was the same for controls and drug-treated worms. Five drug-resistant mutants (T(1)14, T(2)2, T(2)16, and T(2)26) were isolated following ethylmethanesulphonate mutagenesis. All were shorter than N2 at 96 hr on drug-free medium; their growth was not further impaired by either of the anthelmintic drugs. All except T(1)14 exhibited a normal pattern of sexual maturation. Cultures of T(1)14 at 96 hr contained many immature worms. This mutant also exhibited the most impaired motility, being severely uncoordinated in liquid suspension. The other mutants could swim normally but were noticeably slower than N2. Genetic analysis indicated that each mutant was the result of a single genetic lesion, that the mutants were recessive, and that there were two genes for amidantel resistance (adtl and adt2). In vitro studies on representatives of each class (T(1)14 and T(2)2) indicated a defect in the acetylcholine receptor. T(2)2 mutants showed a moderate decrease in sensitivity towards typical cholinergic agonists as well as the anthelmintic drugs, while T(1)14 mutants were apparently devoid of functional pharmacological acetylcholine receptors.