GENISTEIN DIRECTLY INDUCES CARDIAC CFTR CHLORIDE CURRENT BY A TYROSINE KINASE-INDEPENDENT AND PROTEIN-KINASE A-INDEPENDENT PATHWAY IN GUINEA-PIG VENTRICULAR MYOCYTES

Citation
Ce. Chiang et al., GENISTEIN DIRECTLY INDUCES CARDIAC CFTR CHLORIDE CURRENT BY A TYROSINE KINASE-INDEPENDENT AND PROTEIN-KINASE A-INDEPENDENT PATHWAY IN GUINEA-PIG VENTRICULAR MYOCYTES, Biochemical and biophysical research communications, 235(1), 1997, pp. 74-78
Citations number
25
Categorie Soggetti
Biology,Biophysics
ISSN journal
0006291X
Volume
235
Issue
1
Year of publication
1997
Pages
74 - 78
Database
ISI
SICI code
0006-291X(1997)235:1<74:GDICCC>2.0.ZU;2-L
Abstract
With one-suction electrode voltage-clamp technique, we demonstrated th at genistein, a tyrosine kinase (TK) inhibitor, could directly activat e cystic fibrosis transmembrane regulator (CFTR) chloride current in g uinea pig ventricular myocytes, The activation showed concentration-de pendent effect with the estimated IC50 of 39.7 mu M. Tyrphostin 51, an other TK inhibitor, had no effect, suggesting that genistein's effect might be unrelated to TK inhibition, After the chloride current had be en activated by the maximally elevated intracellular cAMP content by s aturating concentration of isoproterenol, forskolin and IBMX, genistei n could further enhance the current. Pre-treatment with saturating con centration of a specific protein kinase A (PKA) inhibitor, H-89, or ot her protein kinase inhibitors H-8 and H-9 in the perfusate or intracel lularly could not prevent the activation of the current by genistein, suggesting a PKA-independent activity, Furthermore, saturating concent ration of calyculin A, a specific inhibitor of phosphotase 1 and 2A, i n the perfusate or intracellularly could not block genistein's action, It is possible that genistein opens the channels directly or inhibits the dephosphorylation process of CFTR, which is not sensitive calycul in A. (C) 1997 Academic Press.