Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel

Autores
Arias, Hugo Rubén; McCardy, Elizabeth A; Bayer, Erin Z.; Gallagher, Martin J.; Blanton, Michael P.
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Previous studies have established the presence of overlapping binding sites for the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl) diazirine ([ 125 I]TID) within the ion channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting state. These well-characterized NCAs and competitive radioligand binding and photolabeling experiments were employed to better characterize the interaction of the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with the resting AChR. Our experiments yielded what appear to be conflicting results: (i) both ketamine and TCP potentiated [ 125 I]TID photoincorporation into AChR subunits; and (ii) ketamine and TCP had very little effect on [ 14 C]amobarbital binding. Nevertheless, (iii) both ketamine and TCP completely displaced [ 3 H]tetracaine binding (K i s ∼ 20.9 and 2.0 μM, respectively) by a mutually exclusive mechanism. To reconcile these results we propose that, in the resting ion channel, TCP and ketamine bind to a site that is spatially distinct from the TID and barbiturate locus, while tetracaine bridges both binding sites.
Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. University of Florida; Estados Unidos
Fil: McCardy, Elizabeth A. Texas Tech University Health Sciences Center; Estados Unidos
Fil: Bayer, Erin Z.. Texas Tech University Health Sciences Center; Estados Unidos
Fil: Gallagher, Martin J.. Washington University in St. Louis; Estados Unidos
Fil: Blanton, Michael P.. Texas Tech University Health Sciences Center; Estados Unidos
Materia
Conformational States
Equilibrium Binding
Ketamine And Phencyclidine Binding Sites
Photoaffinity Labeling
Torpedo Nicotinic Acetylcholine Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/78992
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/78992
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channelArias, Hugo RubénMcCardy, Elizabeth ABayer, Erin Z.Gallagher, Martin J.Blanton, Michael P.Conformational StatesEquilibrium BindingKetamine And Phencyclidine Binding SitesPhotoaffinity LabelingTorpedo Nicotinic Acetylcholine Receptorhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Previous studies have established the presence of overlapping binding sites for the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl) diazirine ([ 125 I]TID) within the ion channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting state. These well-characterized NCAs and competitive radioligand binding and photolabeling experiments were employed to better characterize the interaction of the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with the resting AChR. Our experiments yielded what appear to be conflicting results: (i) both ketamine and TCP potentiated [ 125 I]TID photoincorporation into AChR subunits; and (ii) ketamine and TCP had very little effect on [ 14 C]amobarbital binding. Nevertheless, (iii) both ketamine and TCP completely displaced [ 3 H]tetracaine binding (K i s ∼ 20.9 and 2.0 μM, respectively) by a mutually exclusive mechanism. To reconcile these results we propose that, in the resting ion channel, TCP and ketamine bind to a site that is spatially distinct from the TID and barbiturate locus, while tetracaine bridges both binding sites.Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. University of Florida; Estados UnidosFil: McCardy, Elizabeth A. Texas Tech University Health Sciences Center; Estados UnidosFil: Bayer, Erin Z.. Texas Tech University Health Sciences Center; Estados UnidosFil: Gallagher, Martin J.. Washington University in St. Louis; Estados UnidosFil: Blanton, Michael P.. Texas Tech University Health Sciences Center; Estados UnidosElsevier Science Inc2002-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/78992Arias, Hugo Rubén; McCardy, Elizabeth A; Bayer, Erin Z.; Gallagher, Martin J.; Blanton, Michael P.; Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 403; 1; 1-7-2002; 121-1310003-9861CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S000398610200214Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0003-9861(02)00214-Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:53Zoai:ri.conicet.gov.ar:11336/78992instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:38:53.645CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
title Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
spellingShingle Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
Arias, Hugo Rubén
Conformational States
Equilibrium Binding
Ketamine And Phencyclidine Binding Sites
Photoaffinity Labeling
Torpedo Nicotinic Acetylcholine Receptor
title_short Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
title_full Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
title_fullStr Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
title_full_unstemmed Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
title_sort Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel
dc.creator.none.fl_str_mv Arias, Hugo Rubén
McCardy, Elizabeth A
Bayer, Erin Z.
Gallagher, Martin J.
Blanton, Michael P.
author Arias, Hugo Rubén
author_facet Arias, Hugo Rubén
McCardy, Elizabeth A
Bayer, Erin Z.
Gallagher, Martin J.
Blanton, Michael P.
author_role author
author2 McCardy, Elizabeth A
Bayer, Erin Z.
Gallagher, Martin J.
Blanton, Michael P.
author2_role author
author
author
author
dc.subject.none.fl_str_mv Conformational States
Equilibrium Binding
Ketamine And Phencyclidine Binding Sites
Photoaffinity Labeling
Torpedo Nicotinic Acetylcholine Receptor
topic Conformational States
Equilibrium Binding
Ketamine And Phencyclidine Binding Sites
Photoaffinity Labeling
Torpedo Nicotinic Acetylcholine Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Previous studies have established the presence of overlapping binding sites for the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl) diazirine ([ 125 I]TID) within the ion channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting state. These well-characterized NCAs and competitive radioligand binding and photolabeling experiments were employed to better characterize the interaction of the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with the resting AChR. Our experiments yielded what appear to be conflicting results: (i) both ketamine and TCP potentiated [ 125 I]TID photoincorporation into AChR subunits; and (ii) ketamine and TCP had very little effect on [ 14 C]amobarbital binding. Nevertheless, (iii) both ketamine and TCP completely displaced [ 3 H]tetracaine binding (K i s ∼ 20.9 and 2.0 μM, respectively) by a mutually exclusive mechanism. To reconcile these results we propose that, in the resting ion channel, TCP and ketamine bind to a site that is spatially distinct from the TID and barbiturate locus, while tetracaine bridges both binding sites.
Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. University of Florida; Estados Unidos
Fil: McCardy, Elizabeth A. Texas Tech University Health Sciences Center; Estados Unidos
Fil: Bayer, Erin Z.. Texas Tech University Health Sciences Center; Estados Unidos
Fil: Gallagher, Martin J.. Washington University in St. Louis; Estados Unidos
Fil: Blanton, Michael P.. Texas Tech University Health Sciences Center; Estados Unidos
description Previous studies have established the presence of overlapping binding sites for the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl) diazirine ([ 125 I]TID) within the ion channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting state. These well-characterized NCAs and competitive radioligand binding and photolabeling experiments were employed to better characterize the interaction of the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with the resting AChR. Our experiments yielded what appear to be conflicting results: (i) both ketamine and TCP potentiated [ 125 I]TID photoincorporation into AChR subunits; and (ii) ketamine and TCP had very little effect on [ 14 C]amobarbital binding. Nevertheless, (iii) both ketamine and TCP completely displaced [ 3 H]tetracaine binding (K i s ∼ 20.9 and 2.0 μM, respectively) by a mutually exclusive mechanism. To reconcile these results we propose that, in the resting ion channel, TCP and ketamine bind to a site that is spatially distinct from the TID and barbiturate locus, while tetracaine bridges both binding sites.
publishDate 2002
dc.date.none.fl_str_mv 2002-07-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/78992
Arias, Hugo Rubén; McCardy, Elizabeth A; Bayer, Erin Z.; Gallagher, Martin J.; Blanton, Michael P.; Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 403; 1; 1-7-2002; 121-131
0003-9861
CONICET Digital
CONICET
url http://hdl.handle.net/11336/78992
identifier_str_mv Arias, Hugo Rubén; McCardy, Elizabeth A; Bayer, Erin Z.; Gallagher, Martin J.; Blanton, Michael P.; Allosterically linked noncompetitive antagonist binding sites in the resting nicotinic acetylcholine receptor ion channel; Elsevier Science Inc; Archives of Biochemistry and Biophysics; 403; 1; 1-7-2002; 121-131
0003-9861
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S000398610200214X
info:eu-repo/semantics/altIdentifier/doi/10.1016/S0003-9861(02)00214-X
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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