ACCELERATED COMMUNICATION G Protein-Coupled Receptors as Direct Targets of Inhaled Anesthetics

The molecular pharmacology of inhalational anesthetics remains poorly understood. Despite accumulating evidence suggesting that neuronal membrane proteins are potential targets of inhaled anesthetics, most currently favored membrane protein targets lack any direct evidence for anesthetic binding. We report herein the location of the binding site for the inhaled anesthetic halothane at the amino acid residue level of resolution in the ligand binding cavity in a prototypical G proteincoupled receptor, bovine rhodopsin. Tryptophan fluorescence quenching and direct photoaffinity labeling with [ 14 C]halothane suggested an interhelical location of halothane with a stoichi-The mechanisms of general anesthetic action at the molecular level remain poorly understood, despite their use in millions of patients each year. Understanding the molecula

Volatile anesthetic modulation of oligomerization equilibria in a hexameric model peptide

AbstractTo determine if occupancy of interfacial pockets in oligomeric proteins by volatile anesthetic molecules can allosterically regulate oligomerization equilibria, variants of a three-helix bundle peptide able to form higher oligomers were studied with analytical ultracentrifugation, hydrogen exchange and modeling. Halothane shifted the oligomerization equilibria towards the oligomer only in a mutation predicted to create sufficient volume in the hexameric pocket. Other mutations at this residue, predicted to create a too small or too polar pocket, were unaffected by halothane. Inhaled anesthetic modulation of oligomerization interactions is a novel and potentially generalizable biophysical basis for some anesthetic actions