Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells.
Cell Physiol Biochem
; 36(5): 1928-38, 2015.
Article
em En
| MEDLINE
| ID: mdl-26202353
ABSTRACT
BACKGROUND AND AIMS:
There is accumulating evidence that sympathetic nervous hyperactivity contributes to the pathogenesis of glomerular sclerosis independent of blood pressure effects. A previous study showed that α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear. METHODS ANDRESULTS:
We found that α1-AR is expressed in a human mesangial cell line. The α1-AR agonist phenylephrine (PE) induced Ca(2+) influx as well as release from intracellular Ca(2+) stores. Blockade of TRPC6 with siRNA, anti-TRPC6 antibodies and a TRPC blocker attenuated the PE-induced [Ca(2+)]i increase. Additionally, the PE-induced [Ca(2+)]i increase was phospholipase C dependent. Furthermore, PE induced a [Ca(2+)]i increase even when the intracellular Ca(2+) stores were already depleted. This effect was mimicked by an analog of diacylglycerol. These results suggested that, upon α1-AR stimulation, TRPC6 mediates Ca(2+) influx via a receptor-operated Ca(2+) entry mechanism. Finally, TRPC6 contributes to the PE-induced MC proliferation. The mechanisms are associated with the extracellular signal-regulated kinase (ERK) signaling pathway because blockade of TRPC6 and chelation of extracellular Ca(2+) abrogated PE-induced ERK1/2 abrogated PE-induced ERK1/2 phosphorylation.CONCLUSION:
TRPC6 channels are involved in α1-AR activation-induced Ca(2+) entry, which mediates proliferation via ERK signaling in human MCs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article