Pappu A S, Hauser G
J Pharmacol Exp Ther. 1982 Jul;222(1):109-15.
When added to incubations in vitro. (+/-)-propranolol, a cationic amphiphilic drug, causes profound alterations in incorporation of [32P] orthosphosphate into rat cerebral cortex phospholipids. These include increases in the labeling of phosphatidic acid and polyphosphoinositides abd a decrease in the labeling of phosphatidylcholine. Similar changes occurred in a dose-dependent manner in incubations of cerebral cortex mince, prepared from animals injected i.p. 30 min before death with doses of propranolol ranging from 7.5 to 45 mg/kg. All changes in total incorporation and in labeling pattern had disappeared 3 hr after injection, indicating the reversibility of the effect. Repeated injections of low doses of propranolol (7.5 mg/kg) brought about significant changes in the labeling of brain cortex mince phospholipids, and especially a reduction in total incorporation. Addition of propranolol to kidney and liver minces caused reductions in the labeling of phosphatidylcholine and phosphatidylethanolamine and selective increases in the labeling of acidic lipids, restricted to phosphatidic acid in liver and phosphatidylinositol in kidney. After injection of 45 mg of propranolol per kg, but not at 15 mg/kg, some alterations in the labeling pattern were observed in liver and kidney minces. The differential response of tissues to propranolol injections can be explained on the basis of the pharmacokinetics of drug distribution and clearance and metabolic capacities of the tissues. Changes in phospholipid metabolism may be in part responsible for deleterious side effects that can occur during therapy with high doses of propranolol.
当添加到体外培养物中时，阳离子两亲性药物（±）-普萘洛尔会导致[32P]正磷酸盐掺入大鼠大脑皮层磷脂的过程发生深刻变化。这些变化包括磷脂酸和多磷酸肌醇标记增加，以及磷脂酰胆碱标记减少。在用剂量范围为7.5至45mg/kg的普萘洛尔腹腔注射动物30分钟后处死，制备的大脑皮层碎块培养物中，类似的变化呈剂量依赖性发生。注射后3小时，总掺入量和标记模式的所有变化均消失，表明该效应具有可逆性。重复注射低剂量普萘洛尔（7.5mg/kg）会导致大脑皮层碎块磷脂标记发生显著变化，尤其是总掺入量减少。向肾和肝碎块中添加普萘洛尔会导致磷脂酰胆碱和磷脂酰乙醇胺标记减少，酸性脂质标记选择性增加，肝中仅限于磷脂酸，肾中仅限于磷脂酰肌醇。每千克注射45mg普萘洛尔后，但15mg/kg时未出现这种情况，在肾和肝碎块中观察到标记模式有一些变化。组织对普萘洛尔注射的不同反应可以根据药物分布和清除的药代动力学以及组织的代谢能力来解释。磷脂代谢的变化可能部分导致高剂量普萘洛尔治疗期间可能出现的有害副作用。
