Artículo
Differential regulation on human skin fibroblast by α1 adrenergic receptor subtypes
Fecha de publicación:
12/2007
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Biochemical Pharmacology
ISSN:
0006-2952
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
SKIN FIBROBLAST
,
ALPHA RECEPTOR
,
ALPHA 1
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Identificadores
Colecciones
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
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
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