Tatara T
Department of Anesthesiology, Keio University, School of Medicine, Tokyo.
Masui. 1992 Sep;41(9):1419-25.
The action of anesthetic steroid on the GABAA receptor in the postsynaptic membrane has been suggested as a mechanism of steroid anesthesia. Alphaxalone, the main component of althesin, is a strong anesthetic, whereas its analogue, delta 16-alphaxalone is not. The only structural difference between the two is a presence of the double bond in the D ring of delta 16-alphaxalone. The effects of these steroids on the model membrane structure and the hydrogen bonding between lipid membrane and water were examined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) and compared with their anesthetic potencies in goldfish. Alphaxalone decreased the phase-transition temperature from the solid-gel to the liquid-crystal state of DPPC liposome. FTIR showed that alphaxalone molecules released the bound water molecules in the lipid-water interface of D2O-in-CCl4 reversed micelles. delta 16-alphaxalone in high concentration was also an anesthetic in goldfish. It also showed a weak effect on the phase-transition temperature and the hydrogen bond breaking activity. These changes in the membrane properties correlated to the anesthetic potency. These results suggest that anesthetic potency of steroids is related to their action in destabilizing the structures of the water molecules in the macromolecule-water interface and the macromolecules.
麻醉性类固醇作用于突触后膜上的GABAA受体被认为是类固醇麻醉的一种机制。Althesin的主要成分alphaxalone是一种强效麻醉剂，而其类似物δ16-alphaxalone则不是。两者之间唯一的结构差异是δ16-alphaxalone的D环中存在双键。通过差示扫描量热法（DSC）和傅里叶变换红外光谱法（FTIR）研究了这些类固醇对模型膜结构以及脂质膜与水之间氢键的影响，并将其与它们在金鱼中的麻醉效力进行了比较。Alphaxalone降低了二棕榈酰磷脂酰胆碱（DPPC）脂质体从固态凝胶到液晶态的相变温度。FTIR表明，alphaxalone分子释放了CCl4中D2O反胶束脂质-水界面中的结合水分子。高浓度的δ16-alphaxalone在金鱼中也是一种麻醉剂。它对相变温度和氢键破坏活性也显示出微弱的影响。膜性质的这些变化与麻醉效力相关。这些结果表明，类固醇的麻醉效力与其在破坏大分子-水界面和大分子中水分子结构方面的作用有关。
