Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-a...

Autores
Arias, Hugo R.; Ravazzini, Federica; Targowska Duda, Katarzyna M.; Kaczor, Agnieszka A.; Feuerbach, Dominik; Boffi, Juan Carlos; Draczkowski, Piotr; Montag, Dirk; Brown, Brandon M.; Elgoyhen, Ana Belen; Jozwiak, Krzysztof; Puia, Giulia
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
tThe activity of positive allosteric modulators (PAMs) of 7 nicotinic acetylcholine receptors (AChRs),including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) 7, rat(r) 910, h3-containing AChRs, mouse (m) 5-HT3AR, and several glutamate receptors (GluRs)] andvoltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and-amyloid (A) content. The functional results indicate that PAM-2 inhibits h3-containing AChRs(IC50= 26 ± 6 M) with higher potency than that for NR1aNR2B and NR1aNR2A, two NMDA-sensitiveGluRs. PAM-2 affects neither the activity of m5-HT3ARs, GluR5/KA2 (a kainate-sensitive GluR), nor AChE,and PAM-4 does not affect agonist-activated r910 AChRs. Relevant clinical concentrations of PAM-2?4 do not inhibit Nav1.2 and Kv3.1 ion channels. These PAMs slightly enhance the activity of GluR1 andGluR2, two AMPA-sensitive GluRs. PAM-2 does not change the levels of A42in an Alzheimer?s diseasemouse model (i.e., 5XFAD). The molecular docking and dynamics results using the h7 model suggest thatthe active sites for PAM-2 include the intrasubunit (i.e., PNU-120596 locus) and intersubunit sites. Theseresults support our previous study showing that these PAMs are selective for the 7 AChR, and clarifythat the procognitive/promnesic/antidepressant activity of PAM-2 is not mediated by other targets.
Fil: Arias, Hugo R.. California Northstate University; Estados Unidos
Fil: Ravazzini, Federica. Università Degli Studi Di Modena e Reggio Emilia; Argentina
Fil: Targowska Duda, Katarzyna M.. Medical University of Lublin; Polonia
Fil: Kaczor, Agnieszka A.. Medical University of Lublin; Polonia
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
Fil: Boffi, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Draczkowski, Piotr. Medical University of Lublin; Polonia
Fil: Montag, Dirk. Leibniz Institute for Neurobiology; Alemania
Fil: Brown, Brandon M.. University of California; Estados Unidos
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Jozwiak, Krzysztof. Medical University of Lublin; Polonia
Fil: Puia, Giulia. Università Degli Studi Di Modena e Reggio Emilia; Argentina
Materia
Receptores Nicotíncos
Moduladores Alostéricos
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:11336/44252
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/44252
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid contentArias, Hugo R.Ravazzini, FedericaTargowska Duda, Katarzyna M.Kaczor, Agnieszka A.Feuerbach, DominikBoffi, Juan CarlosDraczkowski, PiotrMontag, DirkBrown, Brandon M.Elgoyhen, Ana BelenJozwiak, KrzysztofPuia, GiuliaReceptores NicotíncosModuladores Alostéricoshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1tThe activity of positive allosteric modulators (PAMs) of 7 nicotinic acetylcholine receptors (AChRs),including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) 7, rat(r) 910, h3-containing AChRs, mouse (m) 5-HT3AR, and several glutamate receptors (GluRs)] andvoltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and-amyloid (A) content. The functional results indicate that PAM-2 inhibits h3-containing AChRs(IC50= 26 ± 6 M) with higher potency than that for NR1aNR2B and NR1aNR2A, two NMDA-sensitiveGluRs. PAM-2 affects neither the activity of m5-HT3ARs, GluR5/KA2 (a kainate-sensitive GluR), nor AChE,and PAM-4 does not affect agonist-activated r910 AChRs. Relevant clinical concentrations of PAM-2?4 do not inhibit Nav1.2 and Kv3.1 ion channels. These PAMs slightly enhance the activity of GluR1 andGluR2, two AMPA-sensitive GluRs. PAM-2 does not change the levels of A42in an Alzheimer?s diseasemouse model (i.e., 5XFAD). The molecular docking and dynamics results using the h7 model suggest thatthe active sites for PAM-2 include the intrasubunit (i.e., PNU-120596 locus) and intersubunit sites. Theseresults support our previous study showing that these PAMs are selective for the 7 AChR, and clarifythat the procognitive/promnesic/antidepressant activity of PAM-2 is not mediated by other targets.Fil: Arias, Hugo R.. California Northstate University; Estados UnidosFil: Ravazzini, Federica. Università Degli Studi Di Modena e Reggio Emilia; ArgentinaFil: Targowska Duda, Katarzyna M.. Medical University of Lublin; PoloniaFil: Kaczor, Agnieszka A.. Medical University of Lublin; PoloniaFil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; SuizaFil: Boffi, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Draczkowski, Piotr. Medical University of Lublin; PoloniaFil: Montag, Dirk. Leibniz Institute for Neurobiology; AlemaniaFil: Brown, Brandon M.. University of California; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Jozwiak, Krzysztof. Medical University of Lublin; PoloniaFil: Puia, Giulia. Università Degli Studi Di Modena e Reggio Emilia; ArgentinaPergamon-Elsevier Science Ltd2016-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/44252Arias, Hugo R.; Ravazzini, Federica; Targowska Duda, Katarzyna M.; Kaczor, Agnieszka A.; Feuerbach, Dominik; et al.; Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content; Pergamon-Elsevier Science Ltd; International Journal of Biochemistry and Cellular Biology; 76; 7-2016; 19-301357-2725CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1357272516300930info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biocel.2016.04.015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:39Zoai:ri.conicet.gov.ar:11336/44252instacron: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:34982025-09-29 09:44:40.041CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
title Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
spellingShingle Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
Arias, Hugo R.
Receptores Nicotíncos
Moduladores Alostéricos
title_short Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
title_full Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
title_fullStr Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
title_full_unstemmed Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
title_sort Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
dc.creator.none.fl_str_mv Arias, Hugo R.
Ravazzini, Federica
Targowska Duda, Katarzyna M.
Kaczor, Agnieszka A.
Feuerbach, Dominik
Boffi, Juan Carlos
Draczkowski, Piotr
Montag, Dirk
Brown, Brandon M.
Elgoyhen, Ana Belen
Jozwiak, Krzysztof
Puia, Giulia
author Arias, Hugo R.
author_facet Arias, Hugo R.
Ravazzini, Federica
Targowska Duda, Katarzyna M.
Kaczor, Agnieszka A.
Feuerbach, Dominik
Boffi, Juan Carlos
Draczkowski, Piotr
Montag, Dirk
Brown, Brandon M.
Elgoyhen, Ana Belen
Jozwiak, Krzysztof
Puia, Giulia
author_role author
author2 Ravazzini, Federica
Targowska Duda, Katarzyna M.
Kaczor, Agnieszka A.
Feuerbach, Dominik
Boffi, Juan Carlos
Draczkowski, Piotr
Montag, Dirk
Brown, Brandon M.
Elgoyhen, Ana Belen
Jozwiak, Krzysztof
Puia, Giulia
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Receptores Nicotíncos
Moduladores Alostéricos
topic Receptores Nicotíncos
Moduladores Alostéricos
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv tThe activity of positive allosteric modulators (PAMs) of 7 nicotinic acetylcholine receptors (AChRs),including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) 7, rat(r) 910, h3-containing AChRs, mouse (m) 5-HT3AR, and several glutamate receptors (GluRs)] andvoltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and-amyloid (A) content. The functional results indicate that PAM-2 inhibits h3-containing AChRs(IC50= 26 ± 6 M) with higher potency than that for NR1aNR2B and NR1aNR2A, two NMDA-sensitiveGluRs. PAM-2 affects neither the activity of m5-HT3ARs, GluR5/KA2 (a kainate-sensitive GluR), nor AChE,and PAM-4 does not affect agonist-activated r910 AChRs. Relevant clinical concentrations of PAM-2?4 do not inhibit Nav1.2 and Kv3.1 ion channels. These PAMs slightly enhance the activity of GluR1 andGluR2, two AMPA-sensitive GluRs. PAM-2 does not change the levels of A42in an Alzheimer?s diseasemouse model (i.e., 5XFAD). The molecular docking and dynamics results using the h7 model suggest thatthe active sites for PAM-2 include the intrasubunit (i.e., PNU-120596 locus) and intersubunit sites. Theseresults support our previous study showing that these PAMs are selective for the 7 AChR, and clarifythat the procognitive/promnesic/antidepressant activity of PAM-2 is not mediated by other targets.
Fil: Arias, Hugo R.. California Northstate University; Estados Unidos
Fil: Ravazzini, Federica. Università Degli Studi Di Modena e Reggio Emilia; Argentina
Fil: Targowska Duda, Katarzyna M.. Medical University of Lublin; Polonia
Fil: Kaczor, Agnieszka A.. Medical University of Lublin; Polonia
Fil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; Suiza
Fil: Boffi, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Draczkowski, Piotr. Medical University of Lublin; Polonia
Fil: Montag, Dirk. Leibniz Institute for Neurobiology; Alemania
Fil: Brown, Brandon M.. University of California; Estados Unidos
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Jozwiak, Krzysztof. Medical University of Lublin; Polonia
Fil: Puia, Giulia. Università Degli Studi Di Modena e Reggio Emilia; Argentina
description tThe activity of positive allosteric modulators (PAMs) of 7 nicotinic acetylcholine receptors (AChRs),including 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), 3-furan-2-yl-N-o-tolylacrylamide (PAM-3), and3-furan-2-yl-N-phenylacrylamide (PAM-4), was tested on a variety of ligand- [i.e., human (h) 7, rat(r) 910, h3-containing AChRs, mouse (m) 5-HT3AR, and several glutamate receptors (GluRs)] andvoltage-gated (i.e., sodium and potassium) ion channels, as well as on acetylcholinesterase (AChE) and-amyloid (A) content. The functional results indicate that PAM-2 inhibits h3-containing AChRs(IC50= 26 ± 6 M) with higher potency than that for NR1aNR2B and NR1aNR2A, two NMDA-sensitiveGluRs. PAM-2 affects neither the activity of m5-HT3ARs, GluR5/KA2 (a kainate-sensitive GluR), nor AChE,and PAM-4 does not affect agonist-activated r910 AChRs. Relevant clinical concentrations of PAM-2?4 do not inhibit Nav1.2 and Kv3.1 ion channels. These PAMs slightly enhance the activity of GluR1 andGluR2, two AMPA-sensitive GluRs. PAM-2 does not change the levels of A42in an Alzheimer?s diseasemouse model (i.e., 5XFAD). The molecular docking and dynamics results using the h7 model suggest thatthe active sites for PAM-2 include the intrasubunit (i.e., PNU-120596 locus) and intersubunit sites. Theseresults support our previous study showing that these PAMs are selective for the 7 AChR, and clarifythat the procognitive/promnesic/antidepressant activity of PAM-2 is not mediated by other targets.
publishDate 2016
dc.date.none.fl_str_mv 2016-07
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/11336/44252
Arias, Hugo R.; Ravazzini, Federica; Targowska Duda, Katarzyna M.; Kaczor, Agnieszka A.; Feuerbach, Dominik; et al.; Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content; Pergamon-Elsevier Science Ltd; International Journal of Biochemistry and Cellular Biology; 76; 7-2016; 19-30
1357-2725
CONICET Digital
CONICET
url http://hdl.handle.net/11336/44252
identifier_str_mv Arias, Hugo R.; Ravazzini, Federica; Targowska Duda, Katarzyna M.; Kaczor, Agnieszka A.; Feuerbach, Dominik; et al.; Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content; Pergamon-Elsevier Science Ltd; International Journal of Biochemistry and Cellular Biology; 76; 7-2016; 19-30
1357-2725
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/S1357272516300930
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biocel.2016.04.015
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/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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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