Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp

Autores
Sterin Borda, L.; Orman, Betina; de Couto Pita, Alejandra Karina; Borda, Enri Santiago
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp.
Fil: Sterin Borda, L.. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: de Couto Pita, Alejandra Karina. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
Nitric Oxide
Dental Pulp
Muscarinic Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/13303
Acceder
id CONICETDig_2fd6eb9ae7522dccd688500cbe7525cd
oai_identifier_str oai:ri.conicet.gov.ar:11336/13303
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulpSterin Borda, L.Orman, Betinade Couto Pita, Alejandra KarinaBorda, Enri SantiagoNitric OxideDental PulpMuscarinic Receptorhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp.Fil: Sterin Borda, L.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: de Couto Pita, Alejandra Karina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaElsevier Science Inc2011-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13303Sterin Borda, L.; Orman, Betina; de Couto Pita, Alejandra Karina; Borda, Enri Santiago; Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp; Elsevier Science Inc; Journal Of Endodontics; 37; 2; 2-2011; 185-1900099-2399enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0099239910009295info:eu-repo/semantics/altIdentifier/doi/10.1016/j.joen.2010.11.021info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:01Zoai:ri.conicet.gov.ar:11336/13303instacron: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 09:59:01.613CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
title Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
spellingShingle Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
Sterin Borda, L.
Nitric Oxide
Dental Pulp
Muscarinic Receptor
title_short Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
title_full Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
title_fullStr Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
title_full_unstemmed Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
title_sort Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp
dc.creator.none.fl_str_mv Sterin Borda, L.
Orman, Betina
de Couto Pita, Alejandra Karina
Borda, Enri Santiago
author Sterin Borda, L.
author_facet Sterin Borda, L.
Orman, Betina
de Couto Pita, Alejandra Karina
Borda, Enri Santiago
author_role author
author2 Orman, Betina
de Couto Pita, Alejandra Karina
Borda, Enri Santiago
author2_role author
author
author
dc.subject.none.fl_str_mv Nitric Oxide
Dental Pulp
Muscarinic Receptor
topic Nitric Oxide
Dental Pulp
Muscarinic Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp.
Fil: Sterin Borda, L.. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: de Couto Pita, Alejandra Karina. Universidad de Buenos Aires. Facultad de Odontología; Argentina
Fil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp.
publishDate 2011
dc.date.none.fl_str_mv 2011-02
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/11336/13303
Sterin Borda, L.; Orman, Betina; de Couto Pita, Alejandra Karina; Borda, Enri Santiago; Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp; Elsevier Science Inc; Journal Of Endodontics; 37; 2; 2-2011; 185-190
0099-2399
url http://hdl.handle.net/11336/13303
identifier_str_mv Sterin Borda, L.; Orman, Betina; de Couto Pita, Alejandra Karina; Borda, Enri Santiago; Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp; Elsevier Science Inc; Journal Of Endodontics; 37; 2; 2-2011; 185-190
0099-2399
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0099239910009295
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.joen.2010.11.021
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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 13.070432

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