Anesthesiology
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Most anesthetics, particularly intravenous agents such as propofol and etomidate, enhance the actions of the neurotransmitter γ-aminobutyric acid (GABA) at the GABA type A receptor. However, there is no agreement as where anesthetics bind to the receptor. A novel approach would be to identify regions on the receptor that are state-dependent, which would account for the ability of anesthetics to affect channel opening by binding differentially to the open and closed states. ⋯ These calculations support the conclusion of a recent photolabeling study that propofol acts at a site at the interface between the extracellular and transmembrane domains, close to the top of transmembrane domain 2.
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Historical Article
Lizzie's Laughing Gas Request on a Dam Family Postcard.
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The authors have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. The study data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. ⋯ These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia, and pain processing.