Measurement of inverse agonism in β-adrenoceptors
- Autores
- Höcht, Christian; Taira, Carlos Alberto; Monczor, Federico
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Increasing numbers of compounds, previously classified as antagonists, were shown to inhibit this spontaneous or constitutive receptor activity, instead of leave it unaffected as expected for a formal antagonist. In addition, some other antagonists did not have any effect by themselves, but prevented the inhibition of constitutive activity induced by thought-to-be antagonists. These thought-to-be antagonists with negative efficacy are now known as “inverse agonists.” Inverse agonism at βAR has been evidenced for both subtypes in wild-type GPCRs systems and in engineered systems with high constitutive activity. It is important to mention that native systems are of particular importance for analyzing the in vivo relevance of constitutive activity because these systems have physiological expression levels of target receptors. Studies of inverse agonism of β blockers in physiological setting have also evidenced that pathophysiological conditions can affect pharmacodynamic properties of these ligands. To date, hundreds of clinically well-known drugs have been tested and classified for this property. Prominent examples include the beta-blockers propranolol, alprenolol, pindolol, and timolol used for treating hypertension, angina pectoris, and arrhythmia that act on the β2ARs, metoprolol, and bisoprolol used for treating hypertension, coronary heart disease, and arrhythmias by acting on β1ARs. Inverse agonists seem to be useful in the treatment of chronic disease characterized by harmful effects resulting from β1AR and β2AR overactivation, such as heart failure and asthma, respectively.
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina - Materia
-
Inverse Agonism
Β-Adrenoceptors
Constitutive Activity
Βar Inverse Agonists
Clinical Potential Uses - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/14170
Ver los metadatos del registro completo
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Measurement of inverse agonism in β-adrenoceptorsHöcht, ChristianTaira, Carlos AlbertoMonczor, FedericoInverse AgonismΒ-AdrenoceptorsConstitutive ActivityΒar Inverse AgonistsClinical Potential Useshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Increasing numbers of compounds, previously classified as antagonists, were shown to inhibit this spontaneous or constitutive receptor activity, instead of leave it unaffected as expected for a formal antagonist. In addition, some other antagonists did not have any effect by themselves, but prevented the inhibition of constitutive activity induced by thought-to-be antagonists. These thought-to-be antagonists with negative efficacy are now known as “inverse agonists.” Inverse agonism at βAR has been evidenced for both subtypes in wild-type GPCRs systems and in engineered systems with high constitutive activity. It is important to mention that native systems are of particular importance for analyzing the in vivo relevance of constitutive activity because these systems have physiological expression levels of target receptors. Studies of inverse agonism of β blockers in physiological setting have also evidenced that pathophysiological conditions can affect pharmacodynamic properties of these ligands. To date, hundreds of clinically well-known drugs have been tested and classified for this property. Prominent examples include the beta-blockers propranolol, alprenolol, pindolol, and timolol used for treating hypertension, angina pectoris, and arrhythmia that act on the β2ARs, metoprolol, and bisoprolol used for treating hypertension, coronary heart disease, and arrhythmias by acting on β1ARs. Inverse agonists seem to be useful in the treatment of chronic disease characterized by harmful effects resulting from β1AR and β2AR overactivation, such as heart failure and asthma, respectively.Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaElsevier Inc2010-12info: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/11336/14170Höcht, Christian; Taira, Carlos Alberto; Monczor, Federico; Measurement of inverse agonism in β-adrenoceptors; Elsevier Inc; Methods In Enzymology.; 485; 12-2010; 37-600076-6879enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/B9780123812964000038info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/B978-0-12-381296-4.00003-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:52:02Zoai:ri.conicet.gov.ar:11336/14170instacron: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 09:52:03.257CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Measurement of inverse agonism in β-adrenoceptors |
title |
Measurement of inverse agonism in β-adrenoceptors |
spellingShingle |
Measurement of inverse agonism in β-adrenoceptors Höcht, Christian Inverse Agonism Β-Adrenoceptors Constitutive Activity Βar Inverse Agonists Clinical Potential Uses |
title_short |
Measurement of inverse agonism in β-adrenoceptors |
title_full |
Measurement of inverse agonism in β-adrenoceptors |
title_fullStr |
Measurement of inverse agonism in β-adrenoceptors |
title_full_unstemmed |
Measurement of inverse agonism in β-adrenoceptors |
title_sort |
Measurement of inverse agonism in β-adrenoceptors |
dc.creator.none.fl_str_mv |
Höcht, Christian Taira, Carlos Alberto Monczor, Federico |
author |
Höcht, Christian |
author_facet |
Höcht, Christian Taira, Carlos Alberto Monczor, Federico |
author_role |
author |
author2 |
Taira, Carlos Alberto Monczor, Federico |
author2_role |
author author |
dc.subject.none.fl_str_mv |
Inverse Agonism Β-Adrenoceptors Constitutive Activity Βar Inverse Agonists Clinical Potential Uses |
topic |
Inverse Agonism Β-Adrenoceptors Constitutive Activity Βar Inverse Agonists Clinical Potential Uses |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Increasing numbers of compounds, previously classified as antagonists, were shown to inhibit this spontaneous or constitutive receptor activity, instead of leave it unaffected as expected for a formal antagonist. In addition, some other antagonists did not have any effect by themselves, but prevented the inhibition of constitutive activity induced by thought-to-be antagonists. These thought-to-be antagonists with negative efficacy are now known as “inverse agonists.” Inverse agonism at βAR has been evidenced for both subtypes in wild-type GPCRs systems and in engineered systems with high constitutive activity. It is important to mention that native systems are of particular importance for analyzing the in vivo relevance of constitutive activity because these systems have physiological expression levels of target receptors. Studies of inverse agonism of β blockers in physiological setting have also evidenced that pathophysiological conditions can affect pharmacodynamic properties of these ligands. To date, hundreds of clinically well-known drugs have been tested and classified for this property. Prominent examples include the beta-blockers propranolol, alprenolol, pindolol, and timolol used for treating hypertension, angina pectoris, and arrhythmia that act on the β2ARs, metoprolol, and bisoprolol used for treating hypertension, coronary heart disease, and arrhythmias by acting on β1ARs. Inverse agonists seem to be useful in the treatment of chronic disease characterized by harmful effects resulting from β1AR and β2AR overactivation, such as heart failure and asthma, respectively. Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina Fil: Taira, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina |
description |
Increasing numbers of compounds, previously classified as antagonists, were shown to inhibit this spontaneous or constitutive receptor activity, instead of leave it unaffected as expected for a formal antagonist. In addition, some other antagonists did not have any effect by themselves, but prevented the inhibition of constitutive activity induced by thought-to-be antagonists. These thought-to-be antagonists with negative efficacy are now known as “inverse agonists.” Inverse agonism at βAR has been evidenced for both subtypes in wild-type GPCRs systems and in engineered systems with high constitutive activity. It is important to mention that native systems are of particular importance for analyzing the in vivo relevance of constitutive activity because these systems have physiological expression levels of target receptors. Studies of inverse agonism of β blockers in physiological setting have also evidenced that pathophysiological conditions can affect pharmacodynamic properties of these ligands. To date, hundreds of clinically well-known drugs have been tested and classified for this property. Prominent examples include the beta-blockers propranolol, alprenolol, pindolol, and timolol used for treating hypertension, angina pectoris, and arrhythmia that act on the β2ARs, metoprolol, and bisoprolol used for treating hypertension, coronary heart disease, and arrhythmias by acting on β1ARs. Inverse agonists seem to be useful in the treatment of chronic disease characterized by harmful effects resulting from β1AR and β2AR overactivation, such as heart failure and asthma, respectively. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-12 |
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/11336/14170 Höcht, Christian; Taira, Carlos Alberto; Monczor, Federico; Measurement of inverse agonism in β-adrenoceptors; Elsevier Inc; Methods In Enzymology.; 485; 12-2010; 37-60 0076-6879 |
url |
http://hdl.handle.net/11336/14170 |
identifier_str_mv |
Höcht, Christian; Taira, Carlos Alberto; Monczor, Federico; Measurement of inverse agonism in β-adrenoceptors; Elsevier Inc; Methods In Enzymology.; 485; 12-2010; 37-60 0076-6879 |
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/B9780123812964000038 info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1016/B978-0-12-381296-4.00003-8 |
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 Inc |
publisher.none.fl_str_mv |
Elsevier 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 |
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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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13.070432 |