| Title: | A Caenorhabditis elegans pheromone antagonizes volatile anesthetic action through a go-coupled pathway |
| Author(s): | van Swinderen B; Metz LB; Shebester LD; Crowder CM; |
| Address: | "Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA" |
| DOI: | 10.1093/genetics/161.1.109 |
| ISSN/ISBN: | 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "Volatile anesthetics (VAs) disrupt nervous system function by an ill-defined mechanism with no known specific antagonists. During the course of characterizing the response of the nematode C. elegans to VAs, we discovered that a C. elegans pheromone antagonizes the VA halothane. Acute exposure to pheromone rendered wild-type C. elegans resistant to clinical concentrations of halothane, increasing the EC(50) from 0.43 +/- 0.03 to 0.90 +/- 0.02. C. elegans mutants that disrupt the function of sensory neurons required for the action of the previously characterized dauer pheromone blocked pheromone-induced resistance (Pir) to halothane. Pheromone preparations from loss-of-function mutants of daf-22, a gene required for dauer pheromone production, lacked the halothane-resistance activity, suggesting that dauer and Pir pheromone are identical. However, the pathways for pheromone's effects on dauer formation and VA action were not identical. Not all mutations that alter dauer formation affected the Pir phenotype. Further, mutations in genes not known to be involved in dauer formation completely blocked Pir, including those altering signaling through the G proteins Goalpha and Gqalpha. A model in which sensory neurons transduce the pheromone activity through antagonistic Go and Gq pathways, modulating VA action against neurotransmitter release machinery, is proposed" |
| Keywords: | "Anesthetics, Inhalation/antagonists & inhibitors/metabolism Animals Caenorhabditis elegans/genetics/*metabolism Drug Resistance/genetics GTP-Binding Protein alpha Subunits, Gi-Go Halothane/*antagonists & inhibitors/metabolism Heterotrimeric GTP-Binding Pr;" |
| Notes: | "Medlinevan Swinderen, Bruno Metz, Laura B Shebester, Laynie D Crowder, C Michael eng R01 GM059781/GM/NIGMS NIH HHS/ R01GM-059781/GM/NIGMS NIH HHS/ R01GM-55832/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 2002/05/23 Genetics. 2002 May; 161(1):109-19. doi: 10.1093/genetics/161.1.109" |
