ENHANCED SYNTHESIS DENOVO OF PHOSPHATIDYLINOSITOL IN LYMPHOCYTES TREATED WITH CATIONIC AMPHIPHILIC DRUGS
ENHANCED SYNTHESIS DENOVO OF PHOSPHATIDYLINOSITOL IN LYMPHOCYTES TREATED WITH CATIONIC AMPHIPHILIC DRUGS
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DOI：
10.1042/bj1480471
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发表时间：
1975-01-01
影响因子：
4.1
通讯作者：
MICHELL, RH
中科院分区：
文献类型：
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作者：
ALLAN, D;MICHELL, RH
不同的两亲性阳离子使猪肠系膜小淋巴细胞中PI和甘油掺入磷脂酰肌醇的速率显著增加。这种新的磷脂酰肌醇的合成使细胞内的磷脂酰肌醇浓度在3.5小时内增加了一倍，与[~3H]-或[14C]-甘油标记的磷脂酰肌醇的合成增加相匹配的是，甘油与磷脂酰胆碱、磷脂酰乙醇胺和三酰甘油的掺入减少了大致相同的程度。产生这些效应的两亲性阳离子包括：三氟拉嗪(在约70微米处的一半最大效应)大于氯丙嗪近似异丙嗪大于辛可卡因大于异丙卡因大于芬氟胺大于苯丙胺大于苯丙胺大于可卡因大约是最有效的化合物；最有效的化合物是那些具有最大和最疏水的非极性取代基的化合物。胞外Ca~(2+)浓度在10 nm-1 mM范围内不改变细胞对阳离子的响应。活性的两亲性阳离子与阴离子磷脂相互作用，导致水分散体聚集和/或色谱行为的改变。这些结果表明，两亲性阳离子重新引导甘油脂的合成，可能是由于抑制了磷脂酸盐磷酸水解酶，从而增加了磷脂酰肌醇的合成，而损害了其他甘油脂的合成。
A variety of amphiphilic cations caused very large increases in the rates of incorporation of Pi and glycerol into phosphatidylinositol in pig mesenteric small lymphocytes. This synthesis de novo of phosphatidylinositol led to a doubling of the phosphatidylinositol concentration in the cells within 3.5 h. The increase in synthesis of phosphatidylinositol labelled with [3H]- or [14C]-glycerol was matched by an approximately equivalent decrease in incorporation of glycerol into phosphatidylcholine, phosphatidylethanolamine and triacylglycerol. Amphilic cations which produced these effects included, in order of decreasing effectiveness, trifluoperazine (half-maximal effect at about 70 mum) greater than chlorpromazine approximately promethazine approximately imipramine greater than cinchocaine greater than amethocaine approximately cetyltrimethylammonium greater than fenfluramine greater than amphetamine greater than 2-phenethylamine greater than cocaine approximately procaine; the most effective compounds were those with the largest and most hydrophobic non-polar substituents. The response to cations was not changed by varying the extracellular Ca2+ concentration in the range 10 nm-1mm. The active amphiphilic cations interacted with anionic phospholipids causing aggregation of aqueous dispersions and/or changes in chromatographic behaviour. These results indicate that amphiphilic cations redirect glycerolipid synthesis de novo, probably owing to inhibition of phosphatidate phosphohydrolase, so that phosphatidylinositol synthesis is increased at the expense of other glycerolipids.