EFFECTS OF ANESTHETICS ON MEMBRANE HYDRATION AND FUSION

麻醉剂对膜水合和融合的影响

• 批准号: 3297517
• 负责人: TIMOTHY J O'LEARY
• 金额: $ 7.1万
• 依托单位: AMERICAN REGISTRY OF PATHOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3297517
• 关键词: anesthetics; calcium; calorimetry; chemical hydration; conformation; drug interactions; drug metabolism; fluorescence spectrometry; fluorimetry; general anesthesia; hydrostatic pressure; infrared spectrometry; liposomes; mathematical model; membrane fusion; membrane lipids; membrane structure; neurotransmitter metabolism; phase change; phospholipids; steroids; synaptic vesicles

The long term goal of this research is to elucidate the relationship between the molecular mechanism of anesthesia and the perturbation by general anesthetics of the physical properties of lipid membranes. The specific objectives are to determine whether the incorporation of general anesthetics into artificial lipid membranes (liposomes) affects the rate or extent of bilayer hydration of nonphosphatidylcholine lipids, whether such an effect on hydration is correlated with anesthetic potency, whether such an effect is reversible upon application of hydrostatic pressure, and whether such an effect inhibits the fusion of phospholipid vesicles. Scanning calorimetry, infrared spectroscopy, and fluorescence spectroscopy will be employed to make these determinations. Scanning calorimetry provides a probe for determining the effect of anesthetics on phase transitions, the formation of non-bilayer phases, and, indirectly, membrane hydration. Infrared spectroscopy provides a direct probe for the extent of membrane hydration, and an assessment of the structural perturbation of the lipid bilayer by general anesthetics. In addition, it provides a means for localizing anesthetics within the bilayer. Fluorometry is used to assess the perturbation by general ansesthetics of calcium-induced membrane fusion, using energy transfer between reporter molecules in the lipid bilayer. Measurements of anesthetic effects on membrane phase transitions, hydration, and fusion, will be carried out under both low and high pressure. Finding such effects would make plausible the theory that general anesthetics work by inhibiting the dehydration of presynaptic vesicles within the nerve terminal, fusion of these vesicles with the presynaptic membrane, and neurotransmitter release.

这项研究的长期目标是阐明关系 在麻醉的分子机制和 一般麻醉的物理特性的扰动 脂质膜。 具体目标是确定 是否将一般麻醉剂纳入人造 脂质膜（脂质体）影响双层的速率或程度 非磷脂酰胆碱脂质的水合，无论这种作用是否 在水合上与麻醉效力有关 在施加静静力压力时，效果是可逆的 以及这种作用是否抑制磷脂的融合 囊泡。 扫描量热法，红外光谱和 荧光光谱将用于使这些 确定。 扫描量热法提供了探针 确定麻醉剂对相变的影响， 非双层相的形成，并间接地膜形成 水合。 红外光谱法提供了直接探针 膜水合的程度和评估 脂质双层的结构扰动通过一般麻醉剂。 此外，它提供了一种将麻醉剂定位的方法 双层。 荧光法用于评估通过 使用钙诱导的膜融合的一般的安息术，使用 脂质双层中的记者分子之间的能量转移。 麻醉对膜相的测量 过渡，水合和融合将在两者下进行 低压和高压。 找到这种效果将使合理 通用麻醉剂通过抑制这种理论来起作用 神经末端内突触前囊泡的脱水， 这些囊泡与突触前膜的融合，以及 神经递质释放。