Genistein modifies the activation kinetics and magnitude of phosphorylated wild-type and G551D-CFTR chloride currents.
J Membr Biol
; 188(3): 175-82, 2002 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-12181609
ABSTRACT
We have studied the mechanism by which genistein activates cystic fibrosis transmembrane conductance regulator (CFTR) in CHO cells expressing wild type or G551D-CFTR. In wild-type CHO cells, after exposure to 2.5 microM forskolin, 25 microM genistein induced a further 2-fold and rapid increase of the forskolin-activated CFTR current. In both types of cells, when forskolin was added after genistein preincubation, whole-cell current density was greatly reduced compared to that measured when genistein was added after phosphorylation of CFTR, and all activation kinetic parameters were significantly altered. Genistein had no effect on the adenylate cyclase activity. Our results suggest that the occupancy of a putative genistein binding site is critical for the gating mechanism of CFTR chloride channels, which, depending on the phosphorylation status of the R-domain, drives CFTR either into a refractory state or alternatively to a highly activated state.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colforsin
/
Adenylyl Cyclases
/
Cystic Fibrosis Transmembrane Conductance Regulator
/
Genistein
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
J Membr Biol
Year:
2002
Document type:
Article