000864468 001__ 864468
000864468 005__ 20240625095114.0
000864468 0247_ $$2doi$$a10.1111/bph.14689
000864468 0247_ $$2ISSN$$a0007-1188
000864468 0247_ $$2ISSN$$a0366-0826
000864468 0247_ $$2ISSN$$a1476-5381
000864468 0247_ $$2ISSN$$a2056-8177
000864468 0247_ $$2Handle$$a2128/22868
000864468 0247_ $$2altmetric$$aaltmetric:59865974
000864468 0247_ $$2pmid$$apmid:30981211
000864468 0247_ $$2WOS$$aWOS:000474034600001
000864468 037__ $$aFZJ-2019-04249
000864468 082__ $$a610
000864468 1001_ $$0P:(DE-HGF)0$$aMaleeva, Galyna$$b0
000864468 245__ $$aA photoswitchable GABA receptor channel blocker
000864468 260__ $$aMalden, MA$$bWiley$$c2019
000864468 3367_ $$2DRIVER$$aarticle
000864468 3367_ $$2DataCite$$aOutput Types/Journal article
000864468 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1568870693_27324
000864468 3367_ $$2BibTeX$$aARTICLE
000864468 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000864468 3367_ $$00$$2EndNote$$aJournal Article
000864468 520__ $$aBackground and PurposeAnion‐selective Cys‐loop receptors (GABA and glycine receptors) provide the main inhibitory drive in the CNS. Both types of receptor operate via chloride‐selective ion channels, though with different kinetics, pharmacological profiles, and localization. Disequilibrium in their function leads to a variety of disorders, which are often treated with allosteric modulators. The few available GABA and glycine receptor channel blockers effectively suppress inhibitory currents in neurons, but their systemic administration is highly toxic. With the aim of developing an efficient light‐controllable modulator of GABA receptors, we constructed azobenzene‐nitrazepam (Azo‐NZ1), which is composed of a nitrazepam moiety merged to an azobenzene photoisomerizable group.Experimental ApproachThe experiments were carried out on cultured cells expressing Cys‐loop receptors of known subunit composition and in brain slices using patch‐clamp. Site‐directed mutagenesis and molecular modelling approaches were applied to evaluate the mechanism of action of Azo‐NZ1.Key ResultsAt visible light, being in trans‐configuration, Azo‐NZ1 blocked heteromeric α1/β2/γ2 GABAA receptors, ρ2 GABAA (GABAC), and α2 glycine receptors, whereas switching the compound into cis‐state by UV illumination restored the activity. Azo‐NZ1 successfully photomodulated GABAergic currents recorded from dentate gyrus neurons. We demonstrated that in trans‐configuration, Azo‐NZ1 blocks the Cl‐selective ion pore of GABA receptors interacting mainly with the 2′ level of the TM2 region.Conclusions and ImplicationsAzo‐NZ1 is a soluble light‐driven Cl‐channel blocker, which allows photo‐modulation of the activity induced by anion‐selective Cys‐loop receptors. Azo‐NZ1 is able to control GABAergic postsynaptic currents and provides new opportunities to study inhibitory neurotransmission using patterned illumination.
000864468 536__ $$0G:(DE-HGF)POF3-571$$a571 - Connectivity and Activity (POF3-571)$$cPOF3-571$$fPOF III$$x0
000864468 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x1
000864468 588__ $$aDataset connected to CrossRef
000864468 7001_ $$0P:(DE-HGF)0$$aWutz, Daniel$$b1
000864468 7001_ $$0P:(DE-HGF)0$$aRustler, Karin$$b2
000864468 7001_ $$0P:(DE-HGF)0$$aNin‐Hill, Alba$$b3
000864468 7001_ $$0P:(DE-HGF)0$$aPetukhova, Elena$$b4
000864468 7001_ $$0P:(DE-HGF)0$$aBautista‐Barrufet, Antoni$$b5
000864468 7001_ $$0P:(DE-HGF)0$$aGomila‐Juaneda, Alexandre$$b6
000864468 7001_ $$0P:(DE-HGF)0$$aScholze, Petra$$b7
000864468 7001_ $$0P:(DE-HGF)0$$aPeiretti, Franck$$b8
000864468 7001_ $$0P:(DE-HGF)0$$aRovira, Carme$$b9
000864468 7001_ $$0P:(DE-HGF)0$$aKönig, Burkhard$$b10
000864468 7001_ $$0P:(DE-HGF)0$$aGorostiza, Pau$$b11$$eCorresponding author
000864468 7001_ $$00000-0003-2699-7825$$aBregestovski, Piotr$$b12$$eCorresponding author
000864468 7001_ $$0P:(DE-Juel1)169976$$aAlfonso-Prieto, Mercedes$$b13$$eCorresponding author$$ufzj
000864468 773__ $$0PERI:(DE-600)2029728-2$$a10.1111/bph.14689$$gp. bph.14689$$n15$$p2661-2677$$tBritish journal of pharmacology$$v176$$x1476-5381$$y2019
000864468 8564_ $$uhttps://juser.fz-juelich.de/record/864468/files/Maleeva_et_al-2019-British_Journal_of_Pharmacology.pdf$$yOpenAccess
000864468 8564_ $$uhttps://juser.fz-juelich.de/record/864468/files/Maleeva_et_al-2019-British_Journal_of_Pharmacology.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000864468 909CO $$ooai:juser.fz-juelich.de:864468$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000864468 9101_ $$0I:(DE-588b)1043886400$$6P:(DE-HGF)0$$aAix-Marseille Université$$b0$$kAMU
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a University of Regensburg$$b1
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a University of Regensburg$$b2
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a University of Barcelona$$b3
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Kazan State Medical University$$b4
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Institute for Bioengineering of Catalonia (IBEC)$$b5
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Institute for Bioengineering of Catalonia (IBEC)$$b6
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Medical University Viena$$b7
000864468 9101_ $$0I:(DE-588b)1043886400$$6P:(DE-HGF)0$$aAix-Marseille Université$$b8$$kAMU
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a University of Barcelona$$b9
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a University of Regensburg$$b10
000864468 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$a Institute for Bioengineering of Catalonia (IBEC)$$b11
000864468 9101_ $$0I:(DE-588b)1043886400$$60000-0003-2699-7825$$aAix-Marseille Université$$b12$$kAMU
000864468 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)169976$$aForschungszentrum Jülich$$b13$$kFZJ
000864468 9131_ $$0G:(DE-HGF)POF3-571$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vConnectivity and Activity$$x0
000864468 9131_ $$0G:(DE-HGF)POF3-574$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vTheory, modelling and simulation$$x1
000864468 9141_ $$y2019
000864468 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000864468 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000864468 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000864468 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBRIT J PHARMACOL : 2017
000864468 915__ $$0LIC:(DE-HGF)CCBYNC4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial CC BY-NC 4.0
000864468 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000864468 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000864468 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000864468 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000864468 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000864468 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bBRIT J PHARMACOL : 2017
000864468 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000864468 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000864468 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000864468 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000864468 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000864468 920__ $$lyes
000864468 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0
000864468 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x1
000864468 980__ $$ajournal
000864468 980__ $$aVDB
000864468 980__ $$aUNRESTRICTED
000864468 980__ $$aI:(DE-Juel1)IAS-5-20120330
000864468 980__ $$aI:(DE-Juel1)INM-9-20140121
000864468 9801_ $$aFullTexts