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, 1994Springer
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 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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