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多烯抗生素与薄脂质膜的相互作用。

The interaction of polyene antibiotics with thin lipid membranes.

作者信息

Andreoli T E, Monahan M

出版信息

J Gen Physiol. 1968 Aug;52(2):300-25. doi: 10.1085/jgp.52.2.300.

DOI:10.1085/jgp.52.2.300
PMID:5672005
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2225804/
Abstract

Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (R(m) congruent with 10(8) ohm-cm(2)) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (T(i)) indicate that these membranes are cation-selective (T(Na) congruent with 0.85; T(Cl) congruent with 0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing approximately 36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced R(m) to approximately 10(2) ohm-cm(2); concomitantly, T(Cl) became congruent with0.92. The slope of the line relating log R(m) and log antibiotic concentration was congruent with4.5. Neither nystatin (2 x 10(-5)M) nor amphotericin B (2 x 10(-7)M) had any effect on membrane stability. The antibiotics had no effect on R(m) or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10(-5)M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect R(m) or membrane ionic selectivity. These data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions (Cl(-), acetate), and, to a lesser degree, cations (Na(+), K(+), Li(+)).

摘要

由绵羊红细胞脂质制备的光学黑色薄脂质膜,当浴液含有氯化钠或氯化钾时,具有高直流电阻((R_m)约为(10^8)欧姆·厘米²)。离子迁移数((T_i))表明这些膜具有阳离子选择性((T_{Na})约为(0.85);(T_{Cl})约为(0.15))。这些电学性质与形成膜的脂质溶液中的胆固醇含量无关。制霉菌素以及可能的两性霉素B是含有约36个环原子以及一个游离氨基和羧基的环状多烯抗生素。当用于形成膜的脂质溶液含有等摩尔量的胆固醇和磷脂时,这些抗生素将(R_m)降低至约(10^2)欧姆·厘米²;同时,(T_{Cl})变为约(0.92)。将(\log R_m)与抗生素浓度相关联的直线斜率约为(4.5)。制霉菌素((2×10^{-5}M))和两性霉素B((2×10^{-7}M))均对膜稳定性没有任何影响。当用于形成膜的脂质不含胆固醇时,这些抗生素对(R_m)或膜的选择通透性没有影响。菲律宾菌素((10^{-5}M)),一种具有28个环原子的不带电荷的多烯,会导致显著的膜不稳定性,但不影响(R_m)或膜的离子选择性。这些数据表明,两性霉素B或制霉菌素可能与膜结合的固醇相互作用,形成多分子复合物,从而极大地增强此类膜对阴离子((Cl^-)、醋酸根)以及在较小程度上对阳离子((Na^+)、(K^+)、(Li^+))的通透性。

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本文引用的文献

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Nystatin binding by protoplasts and a particulate fraction of Neurospora crassa, and a basis for the selective toxicity of polyene antifungal antibiotics.制霉菌素与粗糙脉孢菌原生质体及颗粒组分的结合,以及多烯类抗真菌抗生素选择性毒性的基础。
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THE ACTION OF AMPHOTERICIN B ON MYCOPLASMA LAIDLAWII.两性霉素B对莱氏无胆甾原体的作用
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EFFECT OF AMPHOTERICIN B ON THE PERMEABILITY OF THE TOAD BLADDER.两性霉素B对蟾蜍膀胱通透性的影响。
J Clin Invest. 1965 Aug;44(8):1328-42. doi: 10.1172/JCI105238.
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PENETRATION OF LIPID MONOLAYERS BY POLYENE ANTIBIOTICS. CORRELATION WITH SELECTIVE TOXICITY AND MODE OF ACTION.多烯抗生素对脂质单分子层的穿透作用。与选择性毒性和作用方式的相关性。
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