Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States

Autores
Arias, Hugo Rubén; Gumilar, Fernanda Andrea; Rosenberg, Avraham; Targowska Duda, Katarzyna M.; Feuerbach, Dominik; Jozwiak, Krzysztof; Moaddel, Ruin; Wainer, Irving W.; Bouzat, Cecilia Beatriz
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion: (a) inhibits epibatidine-induced Ca2+ influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with ~100-fold higher potency compared to that in the open state, (c) increases desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits [3H]TCP and [3H]imipramine binding to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/α-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy–driven process, and (f) interacts with a binding domain located between the serine (position 6’) and valine (position 13’) rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.
Fil: Arias, Hugo Rubén. Midwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gumilar, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rosenberg, Avraham. National Institutes of Health; Estados Unidos
Fil: Targowska Duda, Katarzyna M.. Medical University of Lublin; Polonia
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
Fil: Jozwiak, Krzysztof. Medical University of Lublin; Polonia
Fil: Moaddel, Ruin. National Institutes of Health; Estados Unidos
Fil: Wainer, Irving W.. National Institutes of Health; Estados Unidos
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Materia
Antidepressants
Bupropion
Acetylcholine Receptor
Conformational States
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/41912
Acceder
id CONICETDig_e5167e67fd653e6420982465d2cee053
oai_identifier_str oai:ri.conicet.gov.ar:11336/41912
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational StatesArias, Hugo RubénGumilar, Fernanda AndreaRosenberg, AvrahamTargowska Duda, Katarzyna M.Feuerbach, DominikJozwiak, KrzysztofMoaddel, RuinWainer, Irving W.Bouzat, Cecilia BeatrizAntidepressantsBupropionAcetylcholine ReceptorConformational Stateshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion: (a) inhibits epibatidine-induced Ca2+ influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with ~100-fold higher potency compared to that in the open state, (c) increases desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits [3H]TCP and [3H]imipramine binding to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/α-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy–driven process, and (f) interacts with a binding domain located between the serine (position 6’) and valine (position 13’) rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.Fil: Arias, Hugo Rubén. Midwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gumilar, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Rosenberg, Avraham. National Institutes of Health; Estados UnidosFil: Targowska Duda, Katarzyna M.. Medical University of Lublin; PoloniaFil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; SuizaFil: Jozwiak, Krzysztof. Medical University of Lublin; PoloniaFil: Moaddel, Ruin. National Institutes of Health; Estados UnidosFil: Wainer, Irving W.. National Institutes of Health; Estados UnidosFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaAmerican Chemical Society2009-06-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41912Arias, Hugo Rubén; Gumilar, Fernanda Andrea; Rosenberg, Avraham; Targowska Duda, Katarzyna M.; Feuerbach, Dominik; et al.; Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States; American Chemical Society; Biochemistry; 48; 21; 30-6-2009; 4506-45180006-2960CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/bi802206kinfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/bi802206kinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756054/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:03Zoai:ri.conicet.gov.ar:11336/41912instacron: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:34982025-09-03 10:01:03.565CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
title Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
spellingShingle Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
Arias, Hugo Rubén
Antidepressants
Bupropion
Acetylcholine Receptor
Conformational States
title_short Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
title_full Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
title_fullStr Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
title_full_unstemmed Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
title_sort Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States
dc.creator.none.fl_str_mv Arias, Hugo Rubén
Gumilar, Fernanda Andrea
Rosenberg, Avraham
Targowska Duda, Katarzyna M.
Feuerbach, Dominik
Jozwiak, Krzysztof
Moaddel, Ruin
Wainer, Irving W.
Bouzat, Cecilia Beatriz
author Arias, Hugo Rubén
author_facet Arias, Hugo Rubén
Gumilar, Fernanda Andrea
Rosenberg, Avraham
Targowska Duda, Katarzyna M.
Feuerbach, Dominik
Jozwiak, Krzysztof
Moaddel, Ruin
Wainer, Irving W.
Bouzat, Cecilia Beatriz
author_role author
author2 Gumilar, Fernanda Andrea
Rosenberg, Avraham
Targowska Duda, Katarzyna M.
Feuerbach, Dominik
Jozwiak, Krzysztof
Moaddel, Ruin
Wainer, Irving W.
Bouzat, Cecilia Beatriz
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antidepressants
Bupropion
Acetylcholine Receptor
Conformational States
topic Antidepressants
Bupropion
Acetylcholine Receptor
Conformational States
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion: (a) inhibits epibatidine-induced Ca2+ influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with ~100-fold higher potency compared to that in the open state, (c) increases desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits [3H]TCP and [3H]imipramine binding to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/α-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy–driven process, and (f) interacts with a binding domain located between the serine (position 6’) and valine (position 13’) rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.
Fil: Arias, Hugo Rubén. Midwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gumilar, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rosenberg, Avraham. National Institutes of Health; Estados Unidos
Fil: Targowska Duda, Katarzyna M.. Medical University of Lublin; Polonia
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
Fil: Jozwiak, Krzysztof. Medical University of Lublin; Polonia
Fil: Moaddel, Ruin. National Institutes of Health; Estados Unidos
Fil: Wainer, Irving W.. National Institutes of Health; Estados Unidos
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
description To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion: (a) inhibits epibatidine-induced Ca2+ influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with ~100-fold higher potency compared to that in the open state, (c) increases desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits [3H]TCP and [3H]imipramine binding to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/α-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy–driven process, and (f) interacts with a binding domain located between the serine (position 6’) and valine (position 13’) rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.
publishDate 2009
dc.date.none.fl_str_mv 2009-06-30
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/11336/41912
Arias, Hugo Rubén; Gumilar, Fernanda Andrea; Rosenberg, Avraham; Targowska Duda, Katarzyna M.; Feuerbach, Dominik; et al.; Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States; American Chemical Society; Biochemistry; 48; 21; 30-6-2009; 4506-4518
0006-2960
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41912
identifier_str_mv Arias, Hugo Rubén; Gumilar, Fernanda Andrea; Rosenberg, Avraham; Targowska Duda, Katarzyna M.; Feuerbach, Dominik; et al.; Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States; American Chemical Society; Biochemistry; 48; 21; 30-6-2009; 4506-4518
0006-2960
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/bi802206k
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/bi802206k
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756054/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 13.13397

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