Gene Involved in Anesthetic Response Identified

Despite 100 years of trying, scientists have been unable to pin down the molecular targets of an important class of medicines used to anesthetize patients. The medicines, called volatile general anesthetics, are inhaled and spread quickly throughout a patient's bloodstream. The drugs' effects include relieving pain and keeping the patient still during surgery. To better understand how this vital, yet mysterious, group of medicines works, scientists have been hunting for the target molecules in the body that help the drugs induce anesthesia.

For the first time, scientists have found a gene encoding a protein that is required for the effects of the volatile general anesthetics isoflurane and halothane. The gene, called syntaxin, directs the production of a protein that helps communicate electrical impulses in nerve cells. Syntaxin was discovered by Dr. Michael Crowder of Washington University School of Medicine in a worm called C. elegans that is frequently used in laboratory research. An exquisite genetic tool, this tiny worm harbors a nervous system that is very similar to that of humans, but that is much smaller and easier to study. Dr. Crowder and his coworkers are continuing to use this model system to track down other anesthesia-related genes.

The human version of syntaxin is very similar to that of the worm. Moreover, scientists believe that the molecular interactions in which syntaxin participates in the nervous system of worms closely mimic those taking place in humans. Syntaxin is the first gene to be unearthed that is needed to carry out the effects of general anesthetics, and thus may point researchers to molecular targets for anesthesia. This discovery should further scientists' understanding of how anesthesia occurs, as well as perhaps help researchers develop improved anesthetic medicines.

REFERENCE

van Swinderen B, Saifee O, Shebester L, Roberson R, Nonet ML, Crowder CM. A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. Proc Natl Acad Sci USA 1999;96:2479-84.

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