The pharmacological profile of brain liver intestine Na+ channel: inhibition by diarylamidines and activation by fenamates.
Mol Pharmacol
; 80(5): 911-9, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21828194
ABSTRACT
The brain liver intestine Na(+) channel (BLINaC) is a member of the degenerin/epithelial Na(+) channel gene family of unknown function. Elucidation of the physiological function of BLINaC would benefit greatly from pharmacological tools that specifically affect BLINaC activity. Guided by the close molecular relation of BLINaC to acid-sensing ion channels, we discovered in this study that rat BLINaC (rBLINaC) and mouse BLINaC are inhibited by micromolar concentrations of diarylamidines and nafamostat, similar to acid-sensing ion channels. Inhibition was voltage-dependent, suggesting pore block as the mechanism of inhibition. Furthermore, we identified the fenamate flufenamic acid and related compounds as agonists of rBLINaC. Application of millimolar concentrations of flufenamic acid to rBLINaC induced a robust, Na(+)-selective current, which was blocked partially by amiloride. The identification of an artificial agonist of rBLINaC supports the hypothesis that rBLINaC is opened by an unknown physiological ligand. Inhibition by diarylamidines and activation by fenamates define a unique pharmacological profile for BLINaC, which will be useful to unravel the physiological function of this ion channel.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Canais de Sódio
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Bloqueadores dos Canais de Sódio
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Fenamatos
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Mucosa Intestinal
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Fígado
Limite:
Animals
Idioma:
En
Revista:
Mol Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha