Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes

Autores
Sterin, Leonor Josefina; Furlan, César; Orman, Betina; Borda, Enri Santiago
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alpha 1 adrenoceptor (a1-AR) regulation of DNA synthesis was studied in human neonatal foreskin fibroblast. Saturation assay with a specific radioligand for a1 adrenergic [3H]-prazosin revealed two saturated and specific binding sites with high or low affinity. Competitive binding assay with different antagonist subtypes, defined pharmacologically three major types of a1-AR. The a1-AR agonists (from 1 _ 10_10 to 1 _ 10_4 M) triggered a biphasic action on DNA synthesis reaching maximal stimulation at 1 _ 10_9 Mand maximal inhibition at 1 _ 10_6 M. Prazosin, abolished the stimulatory (pA2: 9.24) and inhibitory (pA2:8.80) actions of a1-AR agonists. The a1-AR stimulation resulted in the activation of phosphoinositide turnover (InsP) via phospholipase C (PLC) involving calcium/calmodulin (CaM) and nitric oxide synthase (NOS) that correlates with the DNA synthesis increment; whereas the inhibition resulted in a decrease of cyclic AMP (cAMP) accumulation via adenylate cyclase inhibition. The potency displayed by the specific antagonists tested in binding, DNA synthesis, InsP and NOS at low agonist concentration suggests that they can be elicited by the activation of the same receptor (a1B-AR subtype); while the decrement in DNA synthesis and cAMP at high concentration account by the activation of a1D-AR coupled to Gi protein. Non-functional a1A-AR in neonatal human foreskin fibroblast was observed. Results suggest that the expression of a1-AR subtypes on human skin fibroblast may differentially activate signaling pathways that modulate physiological response of the cells.
Fil: Sterin, Leonor Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Furlan, César. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
SKIN FIBROBLAST
ALPHA RECEPTOR
ALPHA 1
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:11336/241990
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/241990
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypesSterin, Leonor JosefinaFurlan, CésarOrman, BetinaBorda, Enri SantiagoSKIN FIBROBLASTALPHA RECEPTORALPHA 1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Alpha 1 adrenoceptor (a1-AR) regulation of DNA synthesis was studied in human neonatal foreskin fibroblast. Saturation assay with a specific radioligand for a1 adrenergic [3H]-prazosin revealed two saturated and specific binding sites with high or low affinity. Competitive binding assay with different antagonist subtypes, defined pharmacologically three major types of a1-AR. The a1-AR agonists (from 1 _ 10_10 to 1 _ 10_4 M) triggered a biphasic action on DNA synthesis reaching maximal stimulation at 1 _ 10_9 Mand maximal inhibition at 1 _ 10_6 M. Prazosin, abolished the stimulatory (pA2: 9.24) and inhibitory (pA2:8.80) actions of a1-AR agonists. The a1-AR stimulation resulted in the activation of phosphoinositide turnover (InsP) via phospholipase C (PLC) involving calcium/calmodulin (CaM) and nitric oxide synthase (NOS) that correlates with the DNA synthesis increment; whereas the inhibition resulted in a decrease of cyclic AMP (cAMP) accumulation via adenylate cyclase inhibition. The potency displayed by the specific antagonists tested in binding, DNA synthesis, InsP and NOS at low agonist concentration suggests that they can be elicited by the activation of the same receptor (a1B-AR subtype); while the decrement in DNA synthesis and cAMP at high concentration account by the activation of a1D-AR coupled to Gi protein. Non-functional a1A-AR in neonatal human foreskin fibroblast was observed. Results suggest that the expression of a1-AR subtypes on human skin fibroblast may differentially activate signaling pathways that modulate physiological response of the cells.Fil: Sterin, Leonor Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; ArgentinaFil: Furlan, César. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; ArgentinaFil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaPergamon-Elsevier Science Ltd2007-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/241990Sterin, Leonor Josefina; Furlan, César; Orman, Betina; Borda, Enri Santiago; Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 74; 9; 12-2007; 1401-14120006-2952CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(07)00420-0info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2007.06.041info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:30Zoai:ri.conicet.gov.ar:11336/241990instacron: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 09:57:30.898CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
title Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
spellingShingle Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
Sterin, Leonor Josefina
SKIN FIBROBLAST
ALPHA RECEPTOR
ALPHA 1
title_short Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
title_full Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
title_fullStr Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
title_full_unstemmed Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
title_sort Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
dc.creator.none.fl_str_mv Sterin, Leonor Josefina
Furlan, César
Orman, Betina
Borda, Enri Santiago
author Sterin, Leonor Josefina
author_facet Sterin, Leonor Josefina
Furlan, César
Orman, Betina
Borda, Enri Santiago
author_role author
author2 Furlan, César
Orman, Betina
Borda, Enri Santiago
author2_role author
author
author
dc.subject.none.fl_str_mv SKIN FIBROBLAST
ALPHA RECEPTOR
ALPHA 1
topic SKIN FIBROBLAST
ALPHA RECEPTOR
ALPHA 1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Alpha 1 adrenoceptor (a1-AR) regulation of DNA synthesis was studied in human neonatal foreskin fibroblast. Saturation assay with a specific radioligand for a1 adrenergic [3H]-prazosin revealed two saturated and specific binding sites with high or low affinity. Competitive binding assay with different antagonist subtypes, defined pharmacologically three major types of a1-AR. The a1-AR agonists (from 1 _ 10_10 to 1 _ 10_4 M) triggered a biphasic action on DNA synthesis reaching maximal stimulation at 1 _ 10_9 Mand maximal inhibition at 1 _ 10_6 M. Prazosin, abolished the stimulatory (pA2: 9.24) and inhibitory (pA2:8.80) actions of a1-AR agonists. The a1-AR stimulation resulted in the activation of phosphoinositide turnover (InsP) via phospholipase C (PLC) involving calcium/calmodulin (CaM) and nitric oxide synthase (NOS) that correlates with the DNA synthesis increment; whereas the inhibition resulted in a decrease of cyclic AMP (cAMP) accumulation via adenylate cyclase inhibition. The potency displayed by the specific antagonists tested in binding, DNA synthesis, InsP and NOS at low agonist concentration suggests that they can be elicited by the activation of the same receptor (a1B-AR subtype); while the decrement in DNA synthesis and cAMP at high concentration account by the activation of a1D-AR coupled to Gi protein. Non-functional a1A-AR in neonatal human foreskin fibroblast was observed. Results suggest that the expression of a1-AR subtypes on human skin fibroblast may differentially activate signaling pathways that modulate physiological response of the cells.
Fil: Sterin, Leonor Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Furlan, César. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Fil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Alpha 1 adrenoceptor (a1-AR) regulation of DNA synthesis was studied in human neonatal foreskin fibroblast. Saturation assay with a specific radioligand for a1 adrenergic [3H]-prazosin revealed two saturated and specific binding sites with high or low affinity. Competitive binding assay with different antagonist subtypes, defined pharmacologically three major types of a1-AR. The a1-AR agonists (from 1 _ 10_10 to 1 _ 10_4 M) triggered a biphasic action on DNA synthesis reaching maximal stimulation at 1 _ 10_9 Mand maximal inhibition at 1 _ 10_6 M. Prazosin, abolished the stimulatory (pA2: 9.24) and inhibitory (pA2:8.80) actions of a1-AR agonists. The a1-AR stimulation resulted in the activation of phosphoinositide turnover (InsP) via phospholipase C (PLC) involving calcium/calmodulin (CaM) and nitric oxide synthase (NOS) that correlates with the DNA synthesis increment; whereas the inhibition resulted in a decrease of cyclic AMP (cAMP) accumulation via adenylate cyclase inhibition. The potency displayed by the specific antagonists tested in binding, DNA synthesis, InsP and NOS at low agonist concentration suggests that they can be elicited by the activation of the same receptor (a1B-AR subtype); while the decrement in DNA synthesis and cAMP at high concentration account by the activation of a1D-AR coupled to Gi protein. Non-functional a1A-AR in neonatal human foreskin fibroblast was observed. Results suggest that the expression of a1-AR subtypes on human skin fibroblast may differentially activate signaling pathways that modulate physiological response of the cells.
publishDate 2007
dc.date.none.fl_str_mv 2007-12
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/11336/241990
Sterin, Leonor Josefina; Furlan, César; Orman, Betina; Borda, Enri Santiago; Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 74; 9; 12-2007; 1401-1412
0006-2952
CONICET Digital
CONICET
url http://hdl.handle.net/11336/241990
identifier_str_mv Sterin, Leonor Josefina; Furlan, César; Orman, Betina; Borda, Enri Santiago; Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 74; 9; 12-2007; 1401-1412
0006-2952
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://linkinghub.elsevier.com/retrieve/pii/S0006-2952(07)00420-0
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2007.06.041
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
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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score 13.070432

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