Blockade by haloperidol of the increase in tryptophan hydroxylase activity induced by incubation of slices of brain stem with dibutyryl cyclic AMP.

Blockade by haloperidol of the increase in tryptophan hydroxylase activity induced by incubation of slices of brain stem with dibutyryl cyclic AMP.
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氟哌啶醇阻断脑干切片与二丁酰环 AMP 孵育诱导的色氨酸羟化酶活性增加。

DOI:
10.1016/0006-2952(82)90519-6
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发表时间:
1982
影响因子:
5.8
通讯作者:
Boadle-Biber,MC
Boadle-Biber,MC
中科院分区:
医学2区
文献类型:
--
作者:
Boadle-Biber,MC

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用二丁酰环AMP、咖啡因、茶碱和3-异丁基-1-甲基黄嘌呤对大鼠脑干切片进行预处理,可提高脑干切片上清液中色氨酸羟基酶的活性。这种作用似乎不是由环状AMP敏感的机制介导的,因为它不是通过将切片暴露于8-溴环状AMP、非黄嘌呤磷酸二酯酶抑制剂罂粟碱或其他已知的提高组织环状AMP水平的处理来再现的。氟哌啶醇阻止这种酶活性增加的能力与钙调素和钙作为酶激活的媒介的作用是一致的,特别是当这一观察结合证据考虑时,该酶的上清液制剂在磷酸化条件下通过钙-钙调素依赖的过程被激活[5]。然而,鉴于目前实验中使用的氟哌啶醇浓度很高,应该考虑到这种药物可能通过某种其他作用在脑干切片中产生作用,与其与钙调蛋白结合的能力无关。
Pretreatment of rat brain stem slices with dibutyryl cyclic AMP, caffeine, theophylline and 3-isobutyl-1-methylxanthine increased the activity of tryptophan hydroxylase in supernatant preparations of enzyme made from the slices. This effect does not appear to be mediated by a cyclic AMP sensitive mechanism since it was not reproduced by exposure of the slices to 8-bromo cyclic AMP, to papaverine, a nonxanthine phosphodiesterase inhibitor, or to other treatments known to raise tissue cyclic AMP levels. The ability of haloperidol to block this increase in enzyme activity is consistent with a role for calmodulin and calcium as mediators of the enzyme activation, particularly when this observation is considered in conjunction with the evidence that supernatant preparations of this enzyme was activated under phosphorylating conditions by a calcium-calmodulin dependent process [5]. Nevertheless, in view of the high concentrations of haloperidol employed in the present experiments, the possibility that this drug may produce its effects in the brain stem slices through some other action, unrelated to its ability to bind to calmodulin, should be kept in mind.
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