PROPRANOLOL-INDUCED INHIBITION OF RAT-BRAIN CYTOPLASMIC PHOSPHATIDATE PHOSPHOHYDROLASE
PROPRANOLOL-INDUCED INHIBITION OF RAT-BRAIN CYTOPLASMIC PHOSPHATIDATE PHOSPHOHYDROLASE
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DOI：
10.1007/bf00964158
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发表时间：
1983-01-01
影响因子：
4.4
通讯作者：
HAUSER, G
中科院分区：
文献类型：
--
作者：
PAPPU, AS;HAUSER, G
普萘洛尔是一种阳离子两亲性药物，在大鼠大脑皮质糜中引起标记前体掺入磷脂酸及其代谢产物的增强，表明生物合成增加或降解减少。磷脂酸磷酸水解酶的抑制可以解释观察到的药物诱导的磷脂酸和其他酸性脂质蓄积。普萘洛尔对磷脂酸磷酸水解酶的游离和膜结合形式表现出不同的影响。仅当使用膜结合底物时，药物才以剂量依赖性方式抑制细胞质酶。它几乎没有影响的膜结合的酶，无论使用的底物或细胞质酶的性质时，使用游离底物。从腹腔注射普萘洛尔后30分钟处死的大鼠中获得的脑细胞质酶未显示出任何抑制作用。普萘洛尔与细胞膜结合可能会阻止细胞质酶的作用，这可能是通过形成稳定的脂质-药物-蛋白质复合物来降低底物的可用性。
Propranolol, a cationic amiphiphilic drug, caused enhanced incorporation of labeled precursor into phosphatidic acid and its metabolites in rat cerebral cortex mince, suggesting increased biosynthesis or reduced degradation. Inhibition of phosphatidate phosphohydrolase could explain the observed drug-induced accumulation of phosphatidic acid and other acidic lipids. Propranolol exhibited differential effects on the free and membrane-bound forms of phosphatidate phosphohydrolase. The drug inhibited cytoplasmic enzyme in a dose-dependent manner only when membrane-bound substrate was used. It had practically no effect on the membrane-bound enzyme irrespective of the nature of the substrate used or on the cytoplasmic enzyme when free substrate was used. Brain cytoplasmic enzyme obtained from rats sacrificed 30 min after i.p. injections of propranolol did not show any inhibition. Propranolol bound to membranes may prevent cytoplasmic enzyme action, probably by decreasing the availability of substrate through the formation of stable lipid-drug-protein complexes.