INTERACTIONS OF THE LOCAL-ANESTHETIC TETRACAINE WITH MEMBRANES CONTAINING PHOSPHATIDYLCHOLINE AND CHOLESTEROL - A H-2 NMR-STUDY
INTERACTIONS OF THE LOCAL-ANESTHETIC TETRACAINE WITH MEMBRANES CONTAINING PHOSPHATIDYLCHOLINE AND CHOLESTEROL - A H-2 NMR-STUDY
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DOI：
10.1021/bi00413a012
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发表时间：
1988-06-28
期刊：
影响因子：
2.9
通讯作者：
SMITH, ICP
中科院分区：
文献类型：
--
作者：
AUGER, M;JARRELL, HC;SMITH, ICP
本文用特异性的氢化丁卡因、甘油-3-磷酸胆碱(DMPC)和胆固醇的多层分散体，研究了局麻药丁卡因与DMPC和胆固醇的相互作用。实验是在pH值5.5的情况下进行的，当麻醉剂主要带电时，以及在pH 9.5的情况下，麻醉剂主要是不带电的。在含有和不含胆固醇的磷脂酰胆碱双层膜的pH值下，测定了麻醉剂在膜中的分配系数。PH 9.5时较高的分配系数反映了麻醉剂的非荷电形式与双层的碳氢化合物区域之间的疏水相互作用。DMPC/胆固醇体系在两种pH值下的较低分配系数表明，胆固醇增加了脂链的有序性，降低了丁卡因在双层中的溶解度。对于磷脂酰胆碱双分子层，已经提出[Boulanger，Y.，Schreier，S.和Smith，I.C.P.(1981)BioChemical 20,6824-6830]，在低pH下带电的丁卡因主要位于磷脂头基水平，而未带电的丁卡因插入双分子层更深。目前的研究表明丁卡因在含胆固醇的系统中的位置与在纯磷脂酰胆碱双层中的位置不同：麻醉剂位于膜的较高位置。温度升高会导致麻醉剂更深地渗透到双层中。此外，在含有或不含有胆固醇的DMPC双层中掺入麻醉剂，都会导致平台区和酰基链尾部的脂序参数降低，这种影响随着麻醉剂的带电形式而增强。
The interactions of the local anesthetic tetracaine with multilamellar dispersions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol have been investigated by deuterium nuclear magnetic resonance of specifically deuteriated tetracaines, DMPC and cholesterol. Experiments were performed at pH 5.5, when the anesthetic is primarily charged, and at pH 9.5, when it is primarily uncharged. The partition coefficients of the anesthetic in the membrane have been measured at both pH values for phosphatidylcholine bilayers with and without cholesterol. The higher partition coefficients obtained at pH 9.5 reflect the hydrophobic interactions between the uncharged form of the anesthetic and the hydrocarbon region of the bilayer. The lower partition coefficients for the DMPC/cholesterol system at both pH values suggest that cholesterol, which increases the order of the lipid chains, decreases the solubility of tetracaine into the bilayer. For phosphatidylcholine bilayers, it has been proposed [Boulanger, Y., Schreier, S., and Smith, I.C.P. (1981) Biochemistry 20, 6824-6830] that the charged tetracaine at low pH is located mostly at the phospholipid headgroup level while the uncharged tetracaine intercalates more deeply into the bilayer. The present study suggests that the location of tetracaine in the cholesterol-containing system is different from that in pure phosphatidylcholine bilayers: the anesthetic sits higher in the membrane. An increase in temperature results in a deeper penetration of the anesthetic into the bilayer. Moreover, the incorporation of the anesthetic into DMPC bilayers with or without cholesterol results in a reduction of the lipid order parameters both in the plateau and in the tail regions of the acyl chains, this effect being greater with the charged form of the anesthetic.