Moreno-Guzmán M J, Coles G C, Jiménez-González A, Criado-Fornelio A, Ros-Moreno R M, Rodríguez-Caabeiro F
Parasitology and Microbiology Department, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Int J Parasitol. 1998 Mar;28(3):413-8. doi: 10.1016/s0020-7519(97)00198-7.
Larval and adult extracts from isolates of Haemonchus contortus were assayed for specific [3H]levamisole binding activity. All of the tissue preparations displayed [3H]levamisole binding sites. The sensitive isolate SE and resistant isolate RJ showed no differences in larval and adult binding data. Larval SE extracts had higher receptor density (Bmax = 648 fmol mg-1) and dissociation constant (Kd = 1.28 microM) for [3H]levamisole than larval extracts of the American isolate RUSA (Bmax = 87 fmol mg-1 and Kd = 0.15 microM). Extracts of adult SE and RUSA isolates contain as much as 327 fmol mg-1 of protein and 205 fmol mg-1 of protein, respectively, and similar dissociation constants (Kd = 0.77 microM and Kd = 0.81 microM, respectively). There was a good correlation between specific binding activity of larval and adult extracts in both SE and RUSA isolates. The nicotinic cholinergic antagonist alpha-bungarotoxin had no effects in either isolate on [3H]levamisole binding activity. The results confirm that levamisole acts at a cholinergic receptor in H. contortus, and suggest that target site modification could be involved in the development of levamisole resistance.
对捻转血矛线虫分离株的幼虫和成虫提取物进行了特异性[3H]左旋咪唑结合活性检测。所有组织制剂均显示出[3H]左旋咪唑结合位点。敏感分离株SE和抗性分离株RJ在幼虫和成虫结合数据上没有差异。与美国分离株RUSA的幼虫提取物相比，幼虫SE提取物对[3H]左旋咪唑具有更高的受体密度（Bmax = 648 fmol mg-1）和解离常数（Kd = 1.28 microM）（RUSA的Bmax = 87 fmol mg-1，Kd = 0.15 microM）。成年SE和RUSA分离株的提取物分别含有高达327 fmol mg-1的蛋白质和205 fmol mg-1的蛋白质，且解离常数相似（分别为Kd = 0.77 microM和Kd = 0.81 microM）。SE和RUSA分离株的幼虫和成虫提取物的特异性结合活性之间存在良好的相关性。烟碱型胆碱能拮抗剂α-银环蛇毒素对任何一个分离株的[3H]左旋咪唑结合活性均无影响。结果证实左旋咪唑作用于捻转血矛线虫的胆碱能受体，并表明靶位点修饰可能与左旋咪唑抗性的产生有关。
