Effects of calcium channel blocking agents on membrane microviscosity and calcium in the liver of the carbon tetrachloride treated rat.

Effects of calcium channel blocking agents on membrane microviscosity and calcium in the liver of the carbon tetrachloride treated rat.
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钙通道阻断剂对四氯化碳处理大鼠肝脏膜微粘度和钙的影响。

DOI:
10.1016/0006-2952(84)90136-9
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发表时间:
1984
影响因子:
5.8
通讯作者:
Sastry,BV
Sastry,BV
中科院分区:
医学2区
文献类型:
--
作者:
Landon,EJ;Jaiswal,RK;Naukam,RJ;Sastry,BV

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通过四氯化碳处理的大鼠肝脏制备的质膜和微粒体中二苯基己三烯的偏振荧光测定膜微粘度。施用四氯化碳后12至24小时期间其显着降低。在由这些膜制备的脂质体中也观察到微粘度的降低。磷脂含量和磷脂甲基转移酶活性降低,但这些变化似乎并不能解释微粘度的降低。给予四氯化碳后12至24小时,肝细胞中出现大量钙积聚。当在四氯化碳之前施用氯丙嗪、维拉帕米和硝苯地平时,部分减少了随后的钙积累并减少了观察到的组织学损伤的程度。当给予四氯化碳12小时后给予这些药物时,它们并没有减少随后的钙积累。在四氯化碳之前和之后 7 小时施用时,它们对微粘度变化具有微小但可能显着的影响。有人建议,在低水平的微粘度下,可能存在一个临界阈值,低于该阈值,钙进入细胞的控制很差,并且如果在膜微粘度非常低的时候施用,钙通道阻断剂可能无效。组织钙积累与可见的细胞损伤有关。
Membrane microviscosity was determined from the polarized fluorescence of diphenylhexatriene in plasma membranes and microsomes prepared from the liver of carbon tetrachloride treated rats. It was greatly depressed between 12 and 24 hr after the administration of the carbon tetrachloride. Depression of microviscosity was also seen in the liposomes which were prepared from these membranes. There were decreases in phospholipid content and phospholipid methyltransferase activity, but these changes did not appear to explain the decreased microviscosity. A large accumulation of calcium occurred in the liver cells between 12 and 24 hr after the administration of carbon tetrachloride. Chlorpromazine, verapamil and nifedipine, when administered prior to the carbon tetrachloride, partially reduced the later accumulation of calcium and reduced the degree of histological damage observed. When these agents were administered 12 hr after the administration of carbon tetrachloride, they did not reduce the subsequent accumulation of calcium. When administered prior to and 7 hr after carbon tetrachloride, they had a small but potentially significant effect on the microviscosity change. It is suggested that at low levels of microviscosity a critical threshold may exist below which entry of calcium into the cell is poorly controlled and that calcium channel blocking agents may be ineffective if administered at a time when membrane microviscosity is very low. Tissue calcium accumulation was associated with visible cell damage.
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