title: First photoswitchable neurotransmitter transporter inhibitor: light-induced control of γ-aminobutyric acid transporter 1 (GAT1) activity in mouse brain.
abstract: Inhibition of mGAT1, the most abundant GABA transporter in the brain, enhances GABA signaling and alleviates symptoms of CNS disorders such as epilepsy assumed to be associated with low GABA levels. We have now developed a potent and subtype selective photoswitchable inhibitor of this transporter, which for the first time extends the photoswitch concept for the light-induced control of ligand affinity to active membrane transporters. The new inhibitor exhibited reduced activity upon irradiation with light, as demonstrated in GABA uptake assays and electrophysiological experiments with brain slices, and might be used as a tool compound for deepening the understanding of mGAT1 function in brain.
authors.affiliation: Department für Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München , Butenandtstrasse 5-13, 81377 Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Quandt
authors.forename: Georg
authors.initials: G
authors.lastname: Höfner
authors.forename: Jörg
authors.initials: J
authors.lastname: Pabel
authors.forename: Julien
authors.initials: J
authors.lastname: Dine
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Wanner
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D058805:GABA Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D009557:Nipecotic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C000595014:1-(2-(2-(3-(2-(naphthalen-1-yl)diazen-1-yl)phenyl)ethoxy)ethyl)piperidine-3-carboxylic acid; D001391:Azo Compounds; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D009557:Nipecotic Acids