GABA inhibits inhalation anaesthetic-induced membrane fluidization: a spin label study in synaptic and phospholipid membranes.
The hydrophobic interaction of GABA (10(-3)-10(-9) M) with the inhalation anaesthetic enflurane was studied in synaptic plasma membranes of whole rat brain or of the striatum, synaptic mitochondrial membranes and dipalmitoyl lecithin (DPL) vesicles. Stearic acid spin labels, probing either the C-5 level (hydrophilic end) or the C-12 level (hydrophobic end) of the lipid bilayer, were used as indicators of fluidity. Inhalation anaesthetic at 2 mM fluidized the C-5 and the C-12 level of the membranes. A concentration of 0.4 mM produced consistently an increased order (stabilization) at the C-5 level in synaptic plasma membranes. GABA, added prior to the anaesthetic, caused a dose-related inhibition of the anaesthetic-induced fluidization. This restorative effect, which also occurred in DPL vesicles, was not prevented by the GABAA antagonists bicuculline or picrotoxin and was therefore probably not related to receptor mechanisms. When GABA was added after the anaesthetic (2 mM) the inhibition was seen only with 10(-3) M GABA. GABA did not influence (potentiate) the fluidity changes caused by 0.4 mM inhalation anaesthetic in synaptic membranes. Glutamate had a fluidizing effect, but no interaction with enflurane, at the C-5 level of DPL only at a high concentration (10(-3) M). The observed fluidization by enflurane and the restorative effect of GABA, probably through non-receptor-hydrophobic interaction, may be involved in the mechanisms of toxic CNS effects.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D004737:Enflurane / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013113:Spin Labels; D013570:Synaptic Membranes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D008563:Membrane Lipids; D010743:Phospholipids; D013113:Spin Labels; D005680:gamma-Aminobutyric Acid; D004737:Enflurane