Effects of sulphonylureas on cAMP-stimulated Cl− transport via the cystic fibrosis gene product in human epithelial cells
AS Hongre, I Baró, B Berthon, D Escande - Pflügers Archiv, 1994 - Springer
AS Hongre, I Baró, B Berthon, D Escande
Pflügers Archiv, 1994•SpringerThe cystic fibrosis gene product (CFTR) is a Cl− channel that possesses specific binding
sites for cytosolic adenosine triphosphate (ATP) and is activated by cyclic adenosine
monophosphate (cAMP)-dependent protein kinases. We explored the possibility that CFTR
shares a common pharmacology with another ATP-regulated channel protein, the ATP-
sensitive K+ channel that is blocked by sulphonylureas and activated by diazoxide. cAMP-
stimulated Cl− effluxes were measured with 36 Cl− in the epithelial cell line T84 which stably …
sites for cytosolic adenosine triphosphate (ATP) and is activated by cyclic adenosine
monophosphate (cAMP)-dependent protein kinases. We explored the possibility that CFTR
shares a common pharmacology with another ATP-regulated channel protein, the ATP-
sensitive K+ channel that is blocked by sulphonylureas and activated by diazoxide. cAMP-
stimulated Cl− effluxes were measured with 36 Cl− in the epithelial cell line T84 which stably …
Abstract
The cystic fibrosis gene product (CFTR) is a Cl− channel that possesses specific binding sites for cytosolic adenosine triphosphate (ATP) and is activated by cyclic adenosine monophosphate (cAMP)-dependent protein kinases. We explored the possibility that CFTR shares a common pharmacology with another ATP-regulated channel protein, the ATP-sensitive K+ channel that is blocked by sulphonylureas and activated by diazoxide. cAMP-stimulated Cl− effluxes were measured with 36Cl− in the epithelial cell line T84 which stably expresses CFTR. Neither glibenclamide (30 μM), tolbutamide (1 mM) nor diazoxide (100 μM) significantly affected forskolin-activated 36Cl− effluxes in T84 cells. In patch-clamp experiments, glibenclamide exerted only weak inhibitory effects on the whole-cell currents through CFTR with an IC50 of around 0.1 mM. Tolbutamide at 1 mM, but not at 0.1 mM, blocked a current of small amplitude which reversed near the equilibrium potential for K+ ions. We conclude that sulphonylureas and diazoxide are not effective antagonists of endogenous CFTR Cl− channels.
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