Until recently, researchers had a very hazy idea of how commonly used general anesthetics work in the body. In the last few years, however, a number of studies have challenged the traditional opinion that these drugs have no particular molecular target in cells and deaden nerves nonspecifically by seeping into cell membranes. Now, NIGMS grantee Dr. Neil Harrison and his group at the University of Chicago Medical Center, together with scientists at the University of Colorado at Denver and the University of Pennsylvania, have located a site on the surface of nerve cells that is essential for part of the cellular response to two common inhaled anesthetics (enflurane and isoflurane), as well as to alcohol. The site that the researchers identified is part of the receptor for GABA and glycine. GABA and glycine are "inhibitory neurotransmitters" that work by blocking nerve cell messages.
This research may enable scientists to develop safer and more effective anesthetics and, perhaps, a drug that could rapidly reverse the effects of an anesthetic, rendering patients wide awake and alert immediately after surgery. It may also shed light on the molecular site responsible for the unpleasant effects of alcohol--a site that may function less efficiently in alcoholics.
The next step, which the researchers have already begun, is to develop transgenic mice with mutant GABA and glycine receptors in order to look for altered sensitivity to anesthetics and alcohol. This work would provide a conclusive link between the drugs' effects and these neurotransmitter receptors. Eventually, scientists hope to crystallize these proteins and determine both their structure and how anesthetics bind with the proteins to alter their function.
Mihic SJ, Ye Q, Wick M, Koltchine V, Krasowski M, Finn S, Mascia M, Valenzuela CF, Hanson K, Greenblatt E, Harris RA, Harrison N. Sites of alcohol and volatile anaesthetic action on GABA A and glycine receptors. Nature 1997;389:385-9.
Reporters may call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry who can comment on this work.
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8/9/2018 5:47 PM
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