[The anesthetic effects of steroids and their actions on the properties of model membrane].
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.
Tatara
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Department of Anesthesiology, Keio University, School of Medicine, Tokyo.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D006054:Goldfish; D006860:Hydrogen Bonding / Q000187:drug effects; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D011277:Pregnanediones / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013696:Temperature; D014867:Water
D000777:Anesthetics; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D011277:Pregnanediones; D014867:Water; C006477:alphaxalone