Surewicz W K, Leyko W
Biochim Biophys Acta. 1981 May 6;643(2):387-97. doi: 10.1016/0005-2736(81)90083-3.
The interaction of propranolol with model phospholipid membranes was studied using various experimental techniques. The partition coefficient of propranolol in the negatively charged membranes of vesicles prepared from phosphatidylserine and phosphatidic acid was found to be more than 20-times higher than in neutral phosphatidylcholine membranes. Preferential interaction of propranolol with acidic phospholipid membranes was confirmed using the monolayer compression isotherm technique and the spin-labelling method. Phosphatidylserine monolayers were markedly expanded even at a relatively low drug concentration (5 . 10(-6) M). In contrast, the effect of propranolol on phosphatidylcholine monolayers was much smaller, being detectable only at a higher concentration of the drug (1 . 10(-4) M). Spin-labeling experiments show that propranolol exerts marked ordering effect on bilayers prepared from acidic phospholipids and does not change the order parameter of phosphatidylcholine membranes. The dependence of the propranolol fluorescence spectrum on the polarity of the solvent allowed us to identify the intercalation region of the drug in the membrane. The fluorophore moiety of propranolol was found to be localized in the lipid polar head groups region of the bilayer. The role of electrostatic and hydrophobic effects in propranolol-membrane interaction is discussed and the effect of propranolol on the ordering of phospholipid bilayers is compared with the effects of other anesthetic-like molecules.
采用多种实验技术研究了普萘洛尔与模型磷脂膜的相互作用。结果发现，普萘洛尔在由磷脂酰丝氨酸和磷脂酸制备的带负电荷的囊泡膜中的分配系数比在中性磷脂酰胆碱膜中高20多倍。采用单层压缩等温线技术和自旋标记法证实了普萘洛尔与酸性磷脂膜的优先相互作用。即使在相对较低的药物浓度（5×10⁻⁶ M）下，磷脂酰丝氨酸单层也会明显膨胀。相比之下，普萘洛尔对磷脂酰胆碱单层的影响要小得多，只有在较高的药物浓度（1×10⁻⁴ M）下才能检测到。自旋标记实验表明，普萘洛尔对由酸性磷脂制备的双层膜有明显的有序化作用，而不会改变磷脂酰胆碱膜的序参数。普萘洛尔荧光光谱对溶剂极性的依赖性使我们能够确定药物在膜中的插入区域。发现普萘洛尔的荧光团部分位于双层膜的脂质极性头部区域。讨论了静电和疏水作用在普萘洛尔-膜相互作用中的作用，并将普萘洛尔对磷脂双层有序化的影响与其他麻醉样分子的影响进行了比较。
