INHIBITION BY TRIFLUOPERAZINE OF CALMODULIN-INDUCED ACTIVATION OF ATPASE ACTIVITY OF RAT ERYTHROCYTE
INHIBITION BY TRIFLUOPERAZINE OF CALMODULIN-INDUCED ACTIVATION OF ATPASE ACTIVITY OF RAT ERYTHROCYTE
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DOI：
10.1016/0028-3908(80)90134-3
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发表时间：
1980-01-01
影响因子：
4.7
通讯作者：
WEISS, B
中科院分区：
文献类型：
--
作者：
LEVIN, RM;WEISS, B
一种内源性的热稳定钙结合蛋白（钙调素），它能增加环核苷酸磷酸二酯酶的活性，并能选择性地增加大鼠红细胞膜的（Ca ~（2+）+Mg ~（2+））-ATP酶的活性。钙调蛋白激活的ED 50为150 ng钙调蛋白/ml。半最大钙调素诱导的红细胞ATP酶活化所需的Ca 2+浓度为20 μ M，但约为10 μ M。在不存在钙调蛋白的情况下测量的ATP酶的半最大Ca诱导活化需要50 μ M Ca 2+。吩噻嗪三氟拉嗪，它特异性地抑制磷酸二酯酶的激活高亲和力钙特异性结合钙调蛋白，特异性地抑制钙调蛋白诱导的ATP酶的激活。当在钙调蛋白存在下测量时，ATP酶抑制的I50 [中值抑制浓度]为50 μ M，但当在钙调蛋白不存在下测量时，I50 [中值抑制浓度]超过250 μ M。这种三氟拉嗪诱导的ATP酶抑制可以通过加入过量的钙调素来克服。显然，钙调素激活红细胞ATP酶的一种特殊形式，而三氟拉嗪的选择性可能通过与钙调素结合来抑制这种激活。吩噻嗪类抗精神病药的几种生化作用显然可以用一种共同的机制来解释，即，通过选择性地结合钙调蛋白从而抑制其作用。
An endogenous, heat-stable Ca binding protein (calmodulin), which increased the activity of 1 of the forms of cyclic nucleotide phosphodiesterase, increased selectively the activity of a (Ca2+ + Mg2+)-ATPase of rat erythrocyte membranes. The ED50 for calmodulin activation was 150 ng calmodulin/ml. The concentration of Ca2+ required for half-maximum calmodulin-induced activation of erythrocyte ATPase was 20 .mu.M, but .apprx. 50 .mu.M Ca2+ was required for half-maximum Ca-induced activation of ATPase measured in the absence of calmodulin. The phenothiazine trifluoperazine, which specifically inhibits the activation of phosphodiesterase by high-affinity Ca-specific binding to calmodulin, specifically inhibited the calmodulin-induced activation of ATPase. The I50 [median inhibitory concentration] for inhibition of ATPase was 50 .mu.M when measured in the presence of calmodulin but was over 250 .mu.M when measured in its absence. This trifluoperazine-induced inhibition of ATPase could be overcome by adding excess calmodulin. Apparently calmodulin activates a specific form of erythrocyte ATPase and trifluoperazine selectivity inhibits this activation presumably by binding to calmodulin. Several biochemical actions of phenothiazine antipsychotics apparently may be explained by a common mechanism, i.e., by selectively binding to calmodulin and thereby inhibiting its action.