Purzyc L, Całkosiński I
Department of Biochemistry, Wrocław University of Medicine, Poland.
Pol J Pharmacol. 1998 May-Jun;50(3):239-51.
Levamisole, known for a long time as an antiparasitic drug due to its immunomodulating properties, has been used in the therapy of immune disorders. The action of levamisole depends on the dose and the manner of administration, and it seems interesting to establish whether similar dependencies exist for the membrane enzymes of lymphocytes. Ecto-ATPase, the enzyme tightly integrated with cytoplasmic membrane, was chosen to examine these effects. The in vivo studies were conducted on rats with carragenine-induced inflammation. Levamisole was administered at two doses: high (2.5 mg/kg) and low (0.25 mg/kg), according to two schedules: a) at a single dose, simultaneously with carragenine, 24 h before or 24 h after induction of inflammation; the lymphocytes were collected five times every 24 h, and the activity of ecto-ATPase was determined; b) at four doses, every 24 h after carragenine injection; the lymphocytes were collected 120 h after the induction of inflammation. The results of our studies indicate that levamisole reduces the activity of ecto-ATPase in both populations of lymphocytes in vivo. An apparent deactivation of ecto-ATPase of lymphocytes T was observed when high doses of levamisole were administered four times. In the case of a single low dose of levamisole, the deactivating potential of this compound was not so evident, both for lymphocytes B and T. Different reactions of the enzyme from lymphocytes T and B to the levamisole observed in in vivo studies and different effects of inhibitors in vitro, suggest the dissimilarity of the structure of ecto-ATPases from both populations of lymphocytes.
左旋咪唑长期以来因其免疫调节特性而被用作抗寄生虫药物,已被用于免疫紊乱的治疗。左旋咪唑的作用取决于剂量和给药方式,确定淋巴细胞的膜酶是否存在类似的依赖性似乎很有趣。选择与细胞质膜紧密结合的外切ATP酶来研究这些影响。在角叉菜胶诱导炎症的大鼠身上进行体内研究。左旋咪唑按两种剂量给药:高剂量(2.5毫克/千克)和低剂量(0.25毫克/千克),根据两种给药方案:a)单次给药,与角叉菜胶同时给药,在炎症诱导前24小时或诱导后24小时;每24小时收集淋巴细胞5次,并测定外切ATP酶的活性;b)在角叉菜胶注射后每24小时给药4次;在炎症诱导后120小时收集淋巴细胞。我们的研究结果表明,左旋咪唑在体内可降低两种淋巴细胞群体中外切ATP酶的活性。当高剂量的左旋咪唑给药4次时,观察到T淋巴细胞的外切ATP酶明显失活。对于单次低剂量的左旋咪唑,该化合物的失活潜力在B淋巴细胞和T淋巴细胞中都不那么明显。在体内研究中观察到T淋巴细胞和B淋巴细胞的酶对左旋咪唑有不同反应,以及体外抑制剂有不同作用,这表明两种淋巴细胞群体的外切ATP酶结构存在差异。