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Proc Natl Acad Sci U S A
2009 Apr 21;10616:6501-6. doi: 10.1073/pnas.0810590106.
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Identification of a fluorescent general anesthetic, 1-aminoanthracene.
Butts CA
,
Xi J
,
Brannigan G
,
Saad AA
,
Venkatachalan SP
,
Pearce RA
,
Klein ML
,
Eckenhoff RG
,
Dmochowski IJ
.
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We 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 spleenapoferritin (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.
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