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dc.contributor.author
Sterin, Leonor Josefina
dc.contributor.author
Furlan, César
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Orman, Betina
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Borda, Enri Santiago
dc.date.available
2024-08-07T12:46:50Z
dc.date.issued
2007-12
dc.identifier.citation
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
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/241990
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
SKIN FIBROBLAST
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ALPHA RECEPTOR
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ALPHA 1
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Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-08-05T13:49:51Z
dc.journal.volume
74
dc.journal.number
9
dc.journal.pagination
1401-1412
dc.journal.pais
Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Furlan, César. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
dc.description.fil
Fil: Orman, Betina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
dc.description.fil
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
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(07)00420-0
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2007.06.041
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