Anesthetic-membrane interaction: a 2H nuclear magnetic resonance study of the binding of specifically deuterated tetracaine and procaine to phosphatidylcholine.
Anesthetic-membrane interaction: a 2H nuclear magnetic resonance study of the binding of specifically deuterated tetracaine and procaine to phosphatidylcholine.
复制标题
麻醉膜相互作用：特异性氘化丁卡因和普鲁卡因与磷脂酰胆碱结合的 2H 核磁共振研究。
DOI：
10.1139/o84-025
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
I. Smith
中科院分区：
文献类型：
--
作者：
E. C. Kelusky;I. Smith
用~ 2 H核磁共振研究了局部麻醉药丁卡因和普鲁卡因与卵磷脂多层分散体的结合。氘代局麻药的~ 2 H-NMR谱线形状与其达到的平衡状态密切相关。通过反复冻融涡旋循环可以最适当地达到平衡。丁卡因的数据与之前提出的三位点交换模型一致。丁卡因在溶液中在强结合位点和弱结合位点之间缓慢交换，而在弱结合位点和游离位点之间快速交换。根据温度和稀释研究，估计缓慢交换速率在pH 5.5时约为1.5 × 10（3）S-1，在pH 9.5时略快。四极分裂与我们早期的工作在卵磷脂乙醇胺的比较表明，在磷脂酰胆碱的强结合位点的位置是依赖于麻醉剂的电荷。这与卵磷脂酰乙醇胺相反，卵磷脂酰乙醇胺的分子形状似乎是麻醉剂位置的决定因素。质子与模型膜的结合非常弱，只产生宽共振，没有四极分裂。普鲁卡因与丁卡因不同，似乎不受有序酰基链的束缚。
The binding of the local anesthetics tetracaine and procaine with multilamellar dispersions of egg phosphatidylcholine has been studied by 2H nuclear magnetic resonance (NMR). The 2H-NMR line shapes of specifically deuterated local anesthetics are found to be very dependent on the attainment of a true equilibrium. The equilibrium could be most properly reached by the use of repeated freeze-thaw-vortex cycles. The data for tetracaine are consistent with the three-site exchange model proposed earlier. Tetracaine is in slow exchange between a strongly bound site and a weakly bound site and in fast exchange between the weakly bound site and free in solution. The slow exchange rate is estimated, from temperature and dilution studies, to be approximately 1.5 X 10(3) S-1 at pH 5.5 and slightly faster at pH 9.5. Comparisons of the quadrupole splitting with those seen for our earlier work in egg phosphatidylethanolamine suggest that the location of the strongly bound site in phosphatidylcholine is dependent on the anesthetic charge. This is in contrast to egg phosphatidylethanolamine, where molecular shapes appear to be the determining factor for the location of the anesthetic. Procaine bound very weakly to the model membranes, to yield only a broad resonance and no quadrupole splitting. It appears that procaine, unlike tetracaine, is not bound by the ordered acyl chains.