Inhibition of amiloride-sensitive Na+ channel by isothiouronium derivatives.
Am J Physiol
; 271(5 Pt 1): C1457-62, 1996 Nov.
Article
en En
| MEDLINE
| ID: mdl-8944627
ABSTRACT
The effects on the amiloride-blockable Na+ channel of a family of recently synthesized isothiouronium derivatives were measured in plasma membrane vesicles from rat distal colon. Some of these derivatives act as high-affinity Na(+)-like antagonists on the Na(+)-K(+)-adenosinetriphosphatase. One of the reagents tested, 1-bromo-2,4,6-tris(isothiouronium methyl)-benzene tribromide (Br-TITU), was found to be a potent blocker of the Na+ channel. At neutral pH, Br-TITU rapidly inhibits the channel mediated 22Na+ uptake, with an inhibition constant of 94 +/- 39 nM. The inhibition observed is specific and reversible. 1,3-Dibromo-2,4,6-tris(isothiouronium methyl)benzene tribromide and Br-TITU derivatives with methyl and phenyl substitutions on the isothiouronium moiety were much less effective blockers. Incubation of cells with Br-TITU at alkaline (but not neutral) pH produces irreversible inactivation of channels, possibly due ot covalent modification of a lysine residue. This inactivation can be attenuated by amiloride but not by Na+. Thus Br-TITU may be a useful reagent in identifying essential residues of the channel protein.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sodio
/
Canales de Sodio
/
Amilorida
/
Mucosa Intestinal
/
Isotiuronio
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol
Año:
1996
Tipo del documento:
Article
País de afiliación:
Israel