Ondrias K, Biskupic S, Stasko A, Pogády J
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Gen Physiol Biophys. 1992 Aug;11(4):345-57.
The electron spin resonance spectra of 16-doxyl stearic acid (16-SA) incorporated into synaptosomes mostly showed a fluid lipid component and a minor motionally-restricted component (MRC) of the molar fraction of 10-20%, measured at 0 degree C. At 10 mmol/l concentration, thioridazine (TRZ), chlorpromazine (CPZ), chlorprothixene (CPT), perphenazine (PFZ) and levopromazine (LPZ) raised the MRC molar fraction in the synaptosomes to 100, 92, 65, 41 and 39%, respectively (as detected by the spin probe at 0 degrees C). At 4% concentration, TRZ, CPZ, CPT, PFZ, and LPZ the respective MRC percentages were 100, 75, 41, 24 and 17%. In synaptosomal membranes, AMRC splitting values of MRC, induced by TRZ and CPZ, were similar to those of the probe in human serum albumin. MRC induced by CPZ and TRZ was constant (+/- 15%) within the temperature range from 0 to 30 degrees C. At drug/lipid ratios > or = 2 : 1, TRZ and CPZ formed rigid complexes with total lipids isolated from the rat brain. The complexes melted upon increasing the temperature of the samples over 10-20 degrees C. The drugs decreased the lipid concentrations in synaptosomes in the order of potency TRZ > CPZ > CPT > PFZ > or = LPZ; this was similar to their effect on MRC increase. The drugs tested increased the membrane dynamics/disordering, and their potency fairly correlated with their MRC increasing effects. It is supposed that the drug-induced 16-SA probe MRC increase in synaptosomes was a result of mainly decreased lipid/protein ratio in the synaptosomal membranes, which in turn probably is connected with perturbation of lipid-protein interactions and/or membrane proteins. The perturbation of lipid-protein interactions and/or membrane proteins may be connected with the drug perturbation effect on the bulk lipid membrane part.
掺入突触体的16 - 脱氧硬脂酸（16 - SA）的电子自旋共振光谱在0℃测量时，大多显示出一种流动性脂质成分和摩尔分数为10 - 20%的少量运动受限成分（MRC）。在10 mmol/l浓度下，硫利达嗪（TRZ）、氯丙嗪（CPZ）、氯普噻吨（CPT）、奋乃静（PFZ）和左丙嗪（LPZ）使突触体中的MRC摩尔分数分别升至100%、92%、65%、41%和39%（在0℃由自旋探针检测）。在4%浓度下，TRZ、CPZ、CPT、PFZ和LPZ各自的MRC百分比分别为100%、75%、41%、24%和17%。在突触体膜中，TRZ和CPZ诱导的MRC的AMRC分裂值与人血清白蛋白中探针的分裂值相似。CPZ和TRZ诱导的MRC在0至30℃温度范围内是恒定的（±15%）。在药物/脂质比≥2 : 1时，TRZ和CPZ与从大鼠脑分离的总脂质形成刚性复合物。当样品温度升高超过10 - 20℃时，复合物熔化。这些药物降低突触体中脂质浓度的效力顺序为TRZ > CPZ > CPT > PFZ ≥ LPZ；这与其对MRC增加的作用相似。所测试的药物增加了膜动力学/无序性，其效力与它们对MRC增加的作用相当相关。据推测，药物诱导的突触体中16 - SA探针MRC增加主要是突触体膜中脂质/蛋白质比降低的结果，这反过来可能与脂质 - 蛋白质相互作用和/或膜蛋白的扰动有关。脂质 - 蛋白质相互作用和/或膜蛋白的扰动可能与药物对大量脂质膜部分的扰动作用有关。
