Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling

Knowing that cell-surface receptors that recognize and respond to extracellular stimuli are key components for the regular communication between individual cells required for the survival of any living organism, the aim of the present work was to investigate the effect of H2R overexpression on the U...

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Autores principales: Fernández, Natalia C., Mladovan, Alejandro G., Shayo, Carina C.
Publicado: 2006
Materias:
cAMP
Cell differentiation
GRK
Histamine receptors
PDE
Receptor overexpression
amthamine
cyclic AMP
G protein coupled receptor kinase 2
histamine H2 receptor
histamine H2 receptor agonist
phosphodiesterase
rolipram
article
cell differentiation
cell proliferation
concentration response
controlled study
desensitization
enzyme activity
gene overexpression
human
human cell
priority journal
signal transduction
Calcium
Cell Differentiation
Cyclic AMP
Dose-Response Relationship, Drug
Histamine Agonists
Humans
Phosphoric Diester Hydrolases
Radioligand Assay
Receptors, G-Protein-Coupled
Receptors, Histamine H2
Signal Transduction
U937 Cells
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v71_n8_p1219_Monczor
http://hdl.handle.net/20.500.12110/paper_00062952_v71_n8_p1219_Monczor
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paper:paper_00062952_v71_n8_p1219_Monczor
record_format dspace
spelling paper:paper_00062952_v71_n8_p1219_Monczor2023-06-08T14:30:34Z Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling Fernández, Natalia C. Mladovan, Alejandro G. Shayo, Carina C. cAMP Cell differentiation GRK Histamine receptors PDE Receptor overexpression amthamine cyclic AMP G protein coupled receptor kinase 2 histamine H2 receptor histamine H2 receptor agonist phosphodiesterase rolipram article cell differentiation cell proliferation concentration response controlled study desensitization enzyme activity gene overexpression human human cell priority journal signal transduction Calcium Cell Differentiation Cyclic AMP Dose-Response Relationship, Drug Histamine Agonists Humans Phosphoric Diester Hydrolases Radioligand Assay Receptors, G-Protein-Coupled Receptors, Histamine H2 Signal Transduction U937 Cells Knowing that cell-surface receptors that recognize and respond to extracellular stimuli are key components for the regular communication between individual cells required for the survival of any living organism, the aim of the present work was to investigate the effect of H2R overexpression on the U937 signal transduction pathway and its consequences on cell proliferation and differentiation. The overexpression of H2R led to an increase in cAMP basal levels, a leftward shift of agonist concentration-response curves, and similar maximal response to agonist treatment, suggesting that overexpressed H2Rs act as functional spare receptors. In this system cells triggered several mechanisms tending to restore cAMP basal levels to those of the naïve cells. H2R overexpression induced PDE activity stimulation and GRK2 overexpression. In spite of the onset of these regulatory mechanisms, H2 agonist and rolipram treatments induced the terminal differentiation of the H2R overexpressed clone, conversely to the naïve cells. Present findings show that stably H2R overexpression alters cAMP signalling as the result of not only the amounts of second messenger generated but also the activation or upregulation of various components of signalling cascade, leading to an adapted biologically unique system. This adaptation may represent an advantage or a disadvantage, depending on the biological system, but in any case, the existence of compensatory mechanisms should be considered when a clinical treatment is designed. © 2006 Elsevier Inc. All rights reserved. Fil:Fernandez, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mladovan, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Shayo, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v71_n8_p1219_Monczor http://hdl.handle.net/20.500.12110/paper_00062952_v71_n8_p1219_Monczor
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic cAMP
Cell differentiation
GRK
Histamine receptors
PDE
Receptor overexpression
amthamine
cyclic AMP
G protein coupled receptor kinase 2
histamine H2 receptor
histamine H2 receptor agonist
phosphodiesterase
rolipram
article
cell differentiation
cell proliferation
concentration response
controlled study
desensitization
enzyme activity
gene overexpression
human
human cell
priority journal
signal transduction
Calcium
Cell Differentiation
Cyclic AMP
Dose-Response Relationship, Drug
Histamine Agonists
Humans
Phosphoric Diester Hydrolases
Radioligand Assay
Receptors, G-Protein-Coupled
Receptors, Histamine H2
Signal Transduction
U937 Cells
spellingShingle cAMP
Cell differentiation
GRK
Histamine receptors
PDE
Receptor overexpression
amthamine
cyclic AMP
G protein coupled receptor kinase 2
histamine H2 receptor
histamine H2 receptor agonist
phosphodiesterase
rolipram
article
cell differentiation
cell proliferation
concentration response
controlled study
desensitization
enzyme activity
gene overexpression
human
human cell
priority journal
signal transduction
Calcium
Cell Differentiation
Cyclic AMP
Dose-Response Relationship, Drug
Histamine Agonists
Humans
Phosphoric Diester Hydrolases
Radioligand Assay
Receptors, G-Protein-Coupled
Receptors, Histamine H2
Signal Transduction
U937 Cells
Fernández, Natalia C.
Mladovan, Alejandro G.
Shayo, Carina C.
Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
topic_facet cAMP
Cell differentiation
GRK
Histamine receptors
PDE
Receptor overexpression
amthamine
cyclic AMP
G protein coupled receptor kinase 2
histamine H2 receptor
histamine H2 receptor agonist
phosphodiesterase
rolipram
article
cell differentiation
cell proliferation
concentration response
controlled study
desensitization
enzyme activity
gene overexpression
human
human cell
priority journal
signal transduction
Calcium
Cell Differentiation
Cyclic AMP
Dose-Response Relationship, Drug
Histamine Agonists
Humans
Phosphoric Diester Hydrolases
Radioligand Assay
Receptors, G-Protein-Coupled
Receptors, Histamine H2
Signal Transduction
U937 Cells
description Knowing that cell-surface receptors that recognize and respond to extracellular stimuli are key components for the regular communication between individual cells required for the survival of any living organism, the aim of the present work was to investigate the effect of H2R overexpression on the U937 signal transduction pathway and its consequences on cell proliferation and differentiation. The overexpression of H2R led to an increase in cAMP basal levels, a leftward shift of agonist concentration-response curves, and similar maximal response to agonist treatment, suggesting that overexpressed H2Rs act as functional spare receptors. In this system cells triggered several mechanisms tending to restore cAMP basal levels to those of the naïve cells. H2R overexpression induced PDE activity stimulation and GRK2 overexpression. In spite of the onset of these regulatory mechanisms, H2 agonist and rolipram treatments induced the terminal differentiation of the H2R overexpressed clone, conversely to the naïve cells. Present findings show that stably H2R overexpression alters cAMP signalling as the result of not only the amounts of second messenger generated but also the activation or upregulation of various components of signalling cascade, leading to an adapted biologically unique system. This adaptation may represent an advantage or a disadvantage, depending on the biological system, but in any case, the existence of compensatory mechanisms should be considered when a clinical treatment is designed. © 2006 Elsevier Inc. All rights reserved.
author Fernández, Natalia C.
Mladovan, Alejandro G.
Shayo, Carina C.
author_facet Fernández, Natalia C.
Mladovan, Alejandro G.
Shayo, Carina C.
author_sort Fernández, Natalia C.
title Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
title_short Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
title_full Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
title_fullStr Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
title_full_unstemmed Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling
title_sort histamine h2 receptor overexpression induces u937 cell differentiation despite triggered mechanisms to attenuate camp signalling
publishDate 2006
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v71_n8_p1219_Monczor
http://hdl.handle.net/20.500.12110/paper_00062952_v71_n8_p1219_Monczor
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AT mladovanalejandrog histamineh2receptoroverexpressioninducesu937celldifferentiationdespitetriggeredmechanismstoattenuatecampsignalling
AT shayocarinac histamineh2receptoroverexpressioninducesu937celldifferentiationdespitetriggeredmechanismstoattenuatecampsignalling
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