Sigmoidal compression rate-dependence of inert gas narcotic potency in rats: implication for lipid vs. protein theories of inert gas action in the central nervous system

Inert gases at raised pressure exert anaesthetic effects. It is assumed that anaesthesia by the inert gases is fundamentally similar to anaesthesia produced by general anaesthetics. However, do general anaesthetics bind directly to proteins or influence activity by indirectly perturbing membrane lipids still remains a major question. Although the pressure required to achieve anaesthesia with inert gases has been suggested to exert potentially some pressure antagonism per se, this has not been studied yet to our knowledge. We investigated this possibility using nitrogen, argon, and nitrous oxide. Whatever the narcotic agent used, our results showed that the pressure of narcotic required to induce anaesthetic effects increased, as compression rate increased, in a sigmoid fashion rather than in a linear fashion. Evidence for sigmoidal responses vs. linear responses depended of the narcotic potency of the anaesthetic agent used (nitrogen: r(2) = 0.973 vs, r(2) = 0.941; argon: r(2) = 0.971 vs. r(2) = 0.866; nitrous oxide: r(2) = 0.995 vs. r(2) = 0.879). Since a linear antagonism is predicted by Lipid theories, we think it likely that these findings indicate that inert gases bind to a modulatory site of a protein receptor and act as allosteric modulators. Since other workers provided evidence for binding processes using volatile anaesthetics, the present findings could indicate that all classes of general anaesthetics, including inert gases, could act by binding directly to proteins rather than by dissolving in some lipids of the cellular membrane. (C) 1998 Elsevier Science B.V. All rights reserved.