Identification of a fluorescent general anesthetic, 1-aminoanthracene
Identification of a fluorescent general anesthetic, 1-aminoanthracene
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DOI：
10.1073/pnas.0810590106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Dmochowski, Ivan J.
中科院分区：
文献类型：
--
作者：
Butts, Christopher A.;Xi, Jin;Dmochowski, Ivan J.
We identified a fluorophore, 1-aminoanthracene (1-AMA), that is anesthetic, potentiates GABAergic transmission, and gives an appropriate dissociation constant, K-d approximate to 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 (EC50 = 16 mu M) 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.
