Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation

Autores
Díaz, Antonela Susana; Zappia, Carlos Daniel; Rodriguez Gonzalez, Angela Paola; Sahores, Ana; Sosa, Máximo Hernán; Burghi, Valeria; Monczor, Federico; Davio, Carlos Alberto; Fernandez, Natalia Cristina; Shayo, Carina Claudia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Histamine [2-(4-Imidazolyl)-ethylamine] modulates different biological processes, through histamine H1 and H2 receptors, and their respective blockers are widely used in treating allergic and gastric acid-related disorders. Histamine H1 and H2 receptor crossdesensitization and cointernalization induced by its agonists have been previously described. In this study, we show how this crosstalk determines the response to histamine H1 and H2 receptor inverse agonists and how histamine H1 and H2 receptor inverse agonists interfere with the other receptor's response to agonists. By desensitization assays we demonstrate that histamine H1 and H2 receptor inverse agonists induce a crossregulation between both receptors. In this sense, the histamine H1 receptor inverse agonists desensitize the cAMP response to amthamine, a histamine H2 receptor agonist. In turn, histamine H2 receptor inverse agonists interfere with histamine H1 receptor signaling. We also determine that the crossdesensitization induced by histamine H1 or H2 receptor agonists alters the histamine inverse agonists receptor response: activation of histamine H1 receptor affects cAMP response induced by histamine H2 receptor inverse agonists, whereas histamine H2 receptor agonist induces a negative regulation on the anti-inflammatory response of histamine H1 receptor inverse agonists. Binding studies revealed that histamine H1 and H2 receptors cointernalize after stimulus with histamine receptor inverse agonists. In addition, the inhibition of the internalization process prevents receptor crossregulation. Our study provides new insights in the mechanisms of action of histamine H1 and H2 receptors that explain the effect of histamine H1 and H2 receptor inverse agonists and opens up new venues for novel therapeutic applications.
Fil: Díaz, Antonela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Rodriguez Gonzalez, Angela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Sosa, Máximo Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
2,3-TRIFLUORMETILFENILHISTAMINE DIMALEATE (PUBCHEM CID: 71433958)
AMTHAMINE DIHYDROBROMIDE (PUBCHEM CID: 16218912)
CETIRIZINE DIHYDROCHLORIDE (PUBCHEM CID: 55182)
CHLORPHENIRAMINE MALEATE (PUBCHEM CID: 5281068)
CIMETIDINE (PUBCHEM CID: 2756)
DIPHENHYDRAMINE HYDROCHLORIDE (PUBCHEM CID: 8980)
FAMOTIDINE (PUBCHEM CID: 5353622)
GPCR CROSSREGULATION
HISTAMINE H1 RECEPTOR
HISTAMINE H1 RECEPTOR INVERSE AGONISTS
HISTAMINE H2 RECEPTOR
HISTAMINE H2 RECEPTOR INVERSE AGONISTS
MEPYRAMINE MALEATE (PUBCHEM CID: 5284451)
RANITIDINE HYDROCHLORIDE (PUBCHEM CID‎: ‎3033332)
TRIPROLIDINE HYDROCHLORIDE (PUBCHEM CID: 5702129)
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:11336/116821
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/116821
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulationDíaz, Antonela SusanaZappia, Carlos DanielRodriguez Gonzalez, Angela PaolaSahores, AnaSosa, Máximo HernánBurghi, ValeriaMonczor, FedericoDavio, Carlos AlbertoFernandez, Natalia CristinaShayo, Carina Claudia2,3-TRIFLUORMETILFENILHISTAMINE DIMALEATE (PUBCHEM CID: 71433958)AMTHAMINE DIHYDROBROMIDE (PUBCHEM CID: 16218912)CETIRIZINE DIHYDROCHLORIDE (PUBCHEM CID: 55182)CHLORPHENIRAMINE MALEATE (PUBCHEM CID: 5281068)CIMETIDINE (PUBCHEM CID: 2756)DIPHENHYDRAMINE HYDROCHLORIDE (PUBCHEM CID: 8980)FAMOTIDINE (PUBCHEM CID: 5353622)GPCR CROSSREGULATIONHISTAMINE H1 RECEPTORHISTAMINE H1 RECEPTOR INVERSE AGONISTSHISTAMINE H2 RECEPTORHISTAMINE H2 RECEPTOR INVERSE AGONISTSMEPYRAMINE MALEATE (PUBCHEM CID: 5284451)RANITIDINE HYDROCHLORIDE (PUBCHEM CID‎: ‎3033332)TRIPROLIDINE HYDROCHLORIDE (PUBCHEM CID: 5702129)https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Histamine [2-(4-Imidazolyl)-ethylamine] modulates different biological processes, through histamine H1 and H2 receptors, and their respective blockers are widely used in treating allergic and gastric acid-related disorders. Histamine H1 and H2 receptor crossdesensitization and cointernalization induced by its agonists have been previously described. In this study, we show how this crosstalk determines the response to histamine H1 and H2 receptor inverse agonists and how histamine H1 and H2 receptor inverse agonists interfere with the other receptor's response to agonists. By desensitization assays we demonstrate that histamine H1 and H2 receptor inverse agonists induce a crossregulation between both receptors. In this sense, the histamine H1 receptor inverse agonists desensitize the cAMP response to amthamine, a histamine H2 receptor agonist. In turn, histamine H2 receptor inverse agonists interfere with histamine H1 receptor signaling. We also determine that the crossdesensitization induced by histamine H1 or H2 receptor agonists alters the histamine inverse agonists receptor response: activation of histamine H1 receptor affects cAMP response induced by histamine H2 receptor inverse agonists, whereas histamine H2 receptor agonist induces a negative regulation on the anti-inflammatory response of histamine H1 receptor inverse agonists. Binding studies revealed that histamine H1 and H2 receptors cointernalize after stimulus with histamine receptor inverse agonists. In addition, the inhibition of the internalization process prevents receptor crossregulation. Our study provides new insights in the mechanisms of action of histamine H1 and H2 receptors that explain the effect of histamine H1 and H2 receptor inverse agonists and opens up new venues for novel therapeutic applications.Fil: Díaz, Antonela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Rodriguez Gonzalez, Angela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Sosa, Máximo Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaElsevier Science2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/116821Díaz, Antonela Susana; Zappia, Carlos Daniel; Rodriguez Gonzalez, Angela Paola; Sahores, Ana; Sosa, Máximo Hernán; et al.; Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation; Elsevier Science; European Journal of Pharmacology; 847; 3-2019; 42-520014-2999CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014299919300597info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2019.01.026info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:21:23Zoai:ri.conicet.gov.ar:11336/116821instacron: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 10:21:24.131CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
title Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
spellingShingle Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
Díaz, Antonela Susana
2,3-TRIFLUORMETILFENILHISTAMINE DIMALEATE (PUBCHEM CID: 71433958)
AMTHAMINE DIHYDROBROMIDE (PUBCHEM CID: 16218912)
CETIRIZINE DIHYDROCHLORIDE (PUBCHEM CID: 55182)
CHLORPHENIRAMINE MALEATE (PUBCHEM CID: 5281068)
CIMETIDINE (PUBCHEM CID: 2756)
DIPHENHYDRAMINE HYDROCHLORIDE (PUBCHEM CID: 8980)
FAMOTIDINE (PUBCHEM CID: 5353622)
GPCR CROSSREGULATION
HISTAMINE H1 RECEPTOR
HISTAMINE H1 RECEPTOR INVERSE AGONISTS
HISTAMINE H2 RECEPTOR
HISTAMINE H2 RECEPTOR INVERSE AGONISTS
MEPYRAMINE MALEATE (PUBCHEM CID: 5284451)
RANITIDINE HYDROCHLORIDE (PUBCHEM CID‎: ‎3033332)
TRIPROLIDINE HYDROCHLORIDE (PUBCHEM CID: 5702129)
title_short Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
title_full Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
title_fullStr Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
title_full_unstemmed Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
title_sort Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation
dc.creator.none.fl_str_mv Díaz, Antonela Susana
Zappia, Carlos Daniel
Rodriguez Gonzalez, Angela Paola
Sahores, Ana
Sosa, Máximo Hernán
Burghi, Valeria
Monczor, Federico
Davio, Carlos Alberto
Fernandez, Natalia Cristina
Shayo, Carina Claudia
author Díaz, Antonela Susana
author_facet Díaz, Antonela Susana
Zappia, Carlos Daniel
Rodriguez Gonzalez, Angela Paola
Sahores, Ana
Sosa, Máximo Hernán
Burghi, Valeria
Monczor, Federico
Davio, Carlos Alberto
Fernandez, Natalia Cristina
Shayo, Carina Claudia
author_role author
author2 Zappia, Carlos Daniel
Rodriguez Gonzalez, Angela Paola
Sahores, Ana
Sosa, Máximo Hernán
Burghi, Valeria
Monczor, Federico
Davio, Carlos Alberto
Fernandez, Natalia Cristina
Shayo, Carina Claudia
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 2,3-TRIFLUORMETILFENILHISTAMINE DIMALEATE (PUBCHEM CID: 71433958)
AMTHAMINE DIHYDROBROMIDE (PUBCHEM CID: 16218912)
CETIRIZINE DIHYDROCHLORIDE (PUBCHEM CID: 55182)
CHLORPHENIRAMINE MALEATE (PUBCHEM CID: 5281068)
CIMETIDINE (PUBCHEM CID: 2756)
DIPHENHYDRAMINE HYDROCHLORIDE (PUBCHEM CID: 8980)
FAMOTIDINE (PUBCHEM CID: 5353622)
GPCR CROSSREGULATION
HISTAMINE H1 RECEPTOR
HISTAMINE H1 RECEPTOR INVERSE AGONISTS
HISTAMINE H2 RECEPTOR
HISTAMINE H2 RECEPTOR INVERSE AGONISTS
MEPYRAMINE MALEATE (PUBCHEM CID: 5284451)
RANITIDINE HYDROCHLORIDE (PUBCHEM CID‎: ‎3033332)
TRIPROLIDINE HYDROCHLORIDE (PUBCHEM CID: 5702129)
topic 2,3-TRIFLUORMETILFENILHISTAMINE DIMALEATE (PUBCHEM CID: 71433958)
AMTHAMINE DIHYDROBROMIDE (PUBCHEM CID: 16218912)
CETIRIZINE DIHYDROCHLORIDE (PUBCHEM CID: 55182)
CHLORPHENIRAMINE MALEATE (PUBCHEM CID: 5281068)
CIMETIDINE (PUBCHEM CID: 2756)
DIPHENHYDRAMINE HYDROCHLORIDE (PUBCHEM CID: 8980)
FAMOTIDINE (PUBCHEM CID: 5353622)
GPCR CROSSREGULATION
HISTAMINE H1 RECEPTOR
HISTAMINE H1 RECEPTOR INVERSE AGONISTS
HISTAMINE H2 RECEPTOR
HISTAMINE H2 RECEPTOR INVERSE AGONISTS
MEPYRAMINE MALEATE (PUBCHEM CID: 5284451)
RANITIDINE HYDROCHLORIDE (PUBCHEM CID‎: ‎3033332)
TRIPROLIDINE HYDROCHLORIDE (PUBCHEM CID: 5702129)
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Histamine [2-(4-Imidazolyl)-ethylamine] modulates different biological processes, through histamine H1 and H2 receptors, and their respective blockers are widely used in treating allergic and gastric acid-related disorders. Histamine H1 and H2 receptor crossdesensitization and cointernalization induced by its agonists have been previously described. In this study, we show how this crosstalk determines the response to histamine H1 and H2 receptor inverse agonists and how histamine H1 and H2 receptor inverse agonists interfere with the other receptor's response to agonists. By desensitization assays we demonstrate that histamine H1 and H2 receptor inverse agonists induce a crossregulation between both receptors. In this sense, the histamine H1 receptor inverse agonists desensitize the cAMP response to amthamine, a histamine H2 receptor agonist. In turn, histamine H2 receptor inverse agonists interfere with histamine H1 receptor signaling. We also determine that the crossdesensitization induced by histamine H1 or H2 receptor agonists alters the histamine inverse agonists receptor response: activation of histamine H1 receptor affects cAMP response induced by histamine H2 receptor inverse agonists, whereas histamine H2 receptor agonist induces a negative regulation on the anti-inflammatory response of histamine H1 receptor inverse agonists. Binding studies revealed that histamine H1 and H2 receptors cointernalize after stimulus with histamine receptor inverse agonists. In addition, the inhibition of the internalization process prevents receptor crossregulation. Our study provides new insights in the mechanisms of action of histamine H1 and H2 receptors that explain the effect of histamine H1 and H2 receptor inverse agonists and opens up new venues for novel therapeutic applications.
Fil: Díaz, Antonela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Rodriguez Gonzalez, Angela Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Sosa, Máximo Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Histamine [2-(4-Imidazolyl)-ethylamine] modulates different biological processes, through histamine H1 and H2 receptors, and their respective blockers are widely used in treating allergic and gastric acid-related disorders. Histamine H1 and H2 receptor crossdesensitization and cointernalization induced by its agonists have been previously described. In this study, we show how this crosstalk determines the response to histamine H1 and H2 receptor inverse agonists and how histamine H1 and H2 receptor inverse agonists interfere with the other receptor's response to agonists. By desensitization assays we demonstrate that histamine H1 and H2 receptor inverse agonists induce a crossregulation between both receptors. In this sense, the histamine H1 receptor inverse agonists desensitize the cAMP response to amthamine, a histamine H2 receptor agonist. In turn, histamine H2 receptor inverse agonists interfere with histamine H1 receptor signaling. We also determine that the crossdesensitization induced by histamine H1 or H2 receptor agonists alters the histamine inverse agonists receptor response: activation of histamine H1 receptor affects cAMP response induced by histamine H2 receptor inverse agonists, whereas histamine H2 receptor agonist induces a negative regulation on the anti-inflammatory response of histamine H1 receptor inverse agonists. Binding studies revealed that histamine H1 and H2 receptors cointernalize after stimulus with histamine receptor inverse agonists. In addition, the inhibition of the internalization process prevents receptor crossregulation. Our study provides new insights in the mechanisms of action of histamine H1 and H2 receptors that explain the effect of histamine H1 and H2 receptor inverse agonists and opens up new venues for novel therapeutic applications.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
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/11336/116821
Díaz, Antonela Susana; Zappia, Carlos Daniel; Rodriguez Gonzalez, Angela Paola; Sahores, Ana; Sosa, Máximo Hernán; et al.; Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation; Elsevier Science; European Journal of Pharmacology; 847; 3-2019; 42-52
0014-2999
CONICET Digital
CONICET
url http://hdl.handle.net/11336/116821
identifier_str_mv Díaz, Antonela Susana; Zappia, Carlos Daniel; Rodriguez Gonzalez, Angela Paola; Sahores, Ana; Sosa, Máximo Hernán; et al.; Involvement of histamine H1 and H2 receptor inverse agonists in receptor's crossregulation; Elsevier Science; European Journal of Pharmacology; 847; 3-2019; 42-52
0014-2999
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/abs/pii/S0014299919300597
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejphar.2019.01.026
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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