Jang Hye-Ock, Jeong Dong-Keun, Ahn Shin-Ho, Yoon Chang-Dae, Jeong Soo-Cheol, Jin Seong-Deok, Yun Il
Department of Dental Pharmacology and Biophysics, College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, Pusan 602-739, Korea.
J Biochem Mol Biol. 2004 Sep 30;37(5):603-11. doi: 10.5483/bmbrep.2004.37.5.603.
Fluorescence probes located in different membrane regions were used to evaluate the effects of chlorpromazine .HCl on structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and lipid bilayer thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. The experimental procedure was based on the selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In this study, chlorpromazine .HCl decreased the lateral mobility of Py-3-Py in a concentration dependent-manner, showed a greater ordering effect on the inner monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the drug was found to have a clustering effect on membrane proteins.
位于不同膜区域的荧光探针被用于评估盐酸氯丙嗪对从牛大脑皮层分离的突触体细胞膜囊泡(SPMVs)结构参数(跨膜侧向流动性、环形脂质流动性、蛋白质分布和脂质双层厚度)的影响。实验过程基于三硝基苯基基团对1,3 - 二(1 - 芘基)丙烷(Py - 3 - Py)的选择性猝灭、膜蛋白色氨酸到Py - 3 - Py的无辐射能量转移以及Py - 3 - Py单体到1 - 苯胺基萘 - 8 - 磺酸(ANS)的能量转移。在本研究中,盐酸氯丙嗪以浓度依赖方式降低了Py - 3 - Py的侧向流动性,对内膜层的有序化作用比对外膜层更大,以剂量依赖方式降低了环形脂质流动性,并使膜脂质双层收缩。此外,发现该药物对膜蛋白有聚集作用。