Protein crystallography under xenon and nitrous oxide pressure: Comparison with in vivo pharmacology
In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe) and nitrous oxide (N2O) act by blocking the N-methyl-D-aspartate (NMDA) receptor. Using X-ray crystallography, we examined the binding characteristics of these two gases on two soluble proteins as structural models: urate oxidase, which is a prototype of a variety of intracellular globular proteins, and annexin V which possesses structural and functional characteristics that allow it to be considered as a prototype for the NMDA receptor. The structure of these proteins complexed with Xe and N2O were determined. One N2O molecule or one Xe atom binds to the same main site in both proteins. A second subsite is observed for N2O in each case. The gas binding sites are always hydrophobic flexible gas cavities buried within the monomer. Comparison of the effects of Xe and N2O on urate oxidase and annexin V reveals an interesting relationship with the in vivo pharmacological effects of these gases, the ratio of the gas binding sites volume expansion and the ratio of the narcotic potency being similar. Given these data, we propose that alterations of cytosolic globular protein functions by general anesthetics would be responsible for the early stages of anesthesia such as amnesia and hypnosis, while additional alterations of ion-channel membrane receptor functions are required for deeper effects that progress to "surgical" anesthesia.
CNRS UMR 6185, Centre Cyceron.
Posted: 11/03/2006
This article provided by The International Hypnosis Research Institute.
Enter your email address to subscribe to the IHRI Newsletter.
|
Start noticing things in your life that you can be grateful for. This session is one of the most important sessions that we have produced because it will allow you to adopt a way of living that will have incredible positive results.
|
|
Your dominant thoughts become your reality. In fact, your brain and body actually restructure to fit how you think.This session will show you how to change your thoughts and change your life in ways that you’ve probably never imagined.
|
|
Is your life out of control because of excessive reliance of alcohol? Are you reluctant to deal with this addiction in a public setting?Quit drinking in the privacy of your own home and you’ll learn how to strengthen the sober, non-alcoholic you.
|
