Baldenkov G N, Men'shikov M Iu, Feoktistov I A, Tkachuk V A
Biokhimiia. 1985 Jul;50(7):1141-50.
The effects of neurotropic compounds on Ca-binding proteins (calmodulin, troponin C) were investigated. It was shown that the majority of neuroleptics of the phenothiazine group effectively interact with the both proteins and inhibit calmodulin-dependent cyclic nucleotide phosphodiesterase and Ca2+-activated actomyosin. ATPase. Neuroleptics of the butyrophenone group as well as imipramine and diphenehydramine having a low efficiency interact only with calmodulin. Methophenazine, a phenothiazine neuroleptic, being an effective inhibitor of calmodulin and of calmodulin-dependent phosphodiesterase, does not influence troponin C or Ca-dependent actomyosin ATPase. Therefore, this compound may be used as a convenient tool in the study of processes controlled by these Ca-binding proteins. It is concluded that troponin C possesses Ca-dependent sites which bind pharmacological agents structurally similar to that of calmodulin. However, these sites bind pharmacological agents with a low efficiency and exhibit selectivity towards certain drugs. Despite the obvious homology of the both Ca-binding proteins, i.e., calmodulin, troponin C, their effects on the processes under their control appear to be selective.
研究了亲神经化合物对钙结合蛋白(钙调蛋白、肌钙蛋白C)的影响。结果表明,大多数吩噻嗪类抗精神病药物能有效地与这两种蛋白相互作用,并抑制钙调蛋白依赖性环核苷酸磷酸二酯酶和Ca2+激活的肌动球蛋白ATP酶。丁酰苯类抗精神病药物以及效率较低的丙咪嗪和苯海拉明仅与钙调蛋白相互作用。吩噻嗪类抗精神病药物甲硫吩嗪是钙调蛋白和钙调蛋白依赖性磷酸二酯酶的有效抑制剂,对肌钙蛋白C或Ca依赖性肌动球蛋白ATP酶没有影响。因此,该化合物可作为研究这些钙结合蛋白所控制过程的便利工具。得出的结论是,肌钙蛋白C具有与钙调蛋白结构相似的结合药物的钙依赖性位点。然而,这些位点与药物的结合效率较低,且对某些药物具有选择性。尽管这两种钙结合蛋白(即钙调蛋白、肌钙蛋白C)具有明显的同源性,但它们对其控制过程的影响似乎具有选择性。