The effect of anesthetic charge on anesthetic-phospholipid interactions.
The effect of anesthetic charge on anesthetic-phospholipid interactions.
复制标题
麻醉电荷对麻醉剂-磷脂相互作用的影响。
DOI：
10.1016/0005-2736(81)90371-0
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Low,PS
中科院分区：
文献类型：
--
作者：
Davio,SR;Low,PS
据报道，阳离子和非带电形式的叔胺类局部麻醉剂作为神经阻滞剂具有不同的性质和效力。然而，每种形式的局部麻醉剂对不同模型膜系统特性的相对干扰能力尚不清楚。为此，我们用高灵敏度差示扫描量热法研究了不带电的利多卡因(高pH)及其季胺类似物(W49091)对DMPS、DPPE和DPPC脂质体相变性质的影响。我们报道，中性利多卡因与所有三种磷脂的相互作用类似。这种相互作用导致凝胶的液晶相变温度(Tm)降低，相变热(ΔH)增加，熔融协同性略有降低。另一方面，季胺类利多卡因(W49091)只与DMPS发生显著的相互作用，其结果是DMPS的熔融温度降低，ΔH升高，相变的协同性略有降低。这些结果被解释为在DPPE和DPPC相变过程中未带电的利多卡因进入膜。在DMPS的情况下，两种带电形式的利多卡因的流入必须发生在Tm。这些在脂质相变时的麻醉剂通量被认为是导致观察到的各自相变的升高的原因。观察到阳离子形式的利多卡因不会显著改变DPPC和DPPE脂质体的行为，这表明这些脂类不是麻醉剂在神经膜中位置的重要成分。然而，W49091对DMPS性质的戏剧性扰动表明，磷脂酰丝氨酸可能是该抑制部位的一部分。
Cationic and uncharged forms of a tertiary amine local anesthetic are reported to have different properties and potencies as nerve blocking agents. However, the relative capacities of each form of the local anesthetic to perturb the properties of different model membrane systems is unknown. For this reason we have studied the effects of uncharged lidocaine (high pH) and its quaternary amine analogue (W49091) on the phase transition properties of DMPS, DPPE and DPPC liposomes using high-sensitivity differential scanning calorimetry. We report that neutral lidocaine interacts similarly with all three phospholipids. This interaction results in a decrease in the temperature of the gel å liquid crystalline phase transition (T m), an increase in the enthalpy of the transition (ΔH), and a slight decrease in the cooperativity of melting. Quaternary lidocaine (W49091), on the other hand, interacts significantly with only DMPS; the result being again a decrease in the temperature of DMPS melting, an increase in ΔH, and a slight decrease in the cooperativity of the phase transition. These results are interpreted to indicate that uncharged lidocaine enters the membrane during the DPPE and DPPC phase transitions. In the case of DMPS, an influx of both charged forms of lidocaine must occur at T m. These anesthetic fluxes at the lipid's phase transition are suggested to be responsible for the observed elevated enthalpies of the respective transitions. The observation that the cationic form of lidocaine does not significantly modify the behavior of DPPC and DPPE liposomes suggests that these lipids are not important components of the anesthetic's site in nerve membranes. However, the dramatic perturbation of the properties of DMPS by W49091 suggests that phosphatidylserine may comprise part of this inhibitory site.