• Christopher A Butts, Jin Xi, Grace Brannigan, Abdalla A Saad, Srinivasan P Venkatachalan, Robert A Pearce, Michael L Klein, Roderic G Eckenhoff, and Ivan J Dmochowski.
• Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104, USA.
• Proc. Natl. Acad. Sci. U.S.A. 2009 Apr 21;106(16):6501-6.

AbstractWe identified a fluorophore, 1-aminoanthracene (1-AMA), that is anesthetic, potentiates GABAergic transmission, and gives an appropriate dissociation constant, K(d) approximately 0.1 mM, for binding to the general anesthetic site in horse spleen apoferritin (HSAF). 1-AMA fluorescence is enhanced when bound to HSAF. Thus, displacement of 1-AMA from HSAF by other anesthetics attenuates the fluorescence signal and allows determination of K(d), as validated by isothermal titration calorimetry. This provides a unique fluorescence assay for compound screening and anesthetic discovery. Additional electrophysiology experiments in isolated cells indicate that 1-AMA potentiates chloride currents elicited by GABA, similar to many general anesthetics. Furthermore, 1-AMA reversibly immobilizes stage 45-50 Xenopus laevis tadpoles (EC(50) = 16 microM) and fluorescence micrographs show 1-AMA localized to brain and olfactory regions. Thus, 1-AMA provides an unprecedented opportunity for studying general anesthetic distribution in vivo at the cellular and subcellular levels.

43 keywords...

hide…