Research ArticlesNeuroscience

Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

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Science Signaling  31 Mar 2015:
Vol. 8, Issue 370, pp. ra33
DOI: 10.1126/scisignal.2005912

Wake up and smell the ketamine!

Ketamine antagonizes ion channels known as N-methyl-d-aspartate (NMDA) receptors to mediate its effects as an anesthetic; however, ketamine also has other properties, which suggests that it has other targets. Ho et al. found that ketamine activated four mouse olfactory receptors, which are a subfamily of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs). Structural analysis revealed residues that formed a ketamine-binding site in these olfactory receptors, and mutation of nonresponsive olfactory receptors to engineer the ketamine-binding site rendered them responsive to ketamine. Together, these data suggest that members of this family of GPCRs are functional ketamine receptors and provide a means to identify other potential targets of this pleiotropic drug.