PT  - JOURNAL ARTICLE
AU  - Ahmed Chraïbi
AU  - Jean-Daniel Horisberger
TI  - Stimulation of Epithelial Sodium Channel Activity by the Sulfonylurea Glibenclamide
DP  - 1999 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 341--347
VI  - 290
IP  - 1
4099  - http://jpet.aspetjournals.org/content/290/1/341.short
4100  - http://jpet.aspetjournals.org/content/290/1/341.full
SO  - J Pharmacol Exp Ther1999 Jul 01; 290
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) contributes to the regulation of the sodium balance and blood pressure because it mediates a rate-limiting step in sodium transport across the epithelium of the distal nephron. The activity of ENaC is regulated by hormones, such as aldosterone and vasopressin, and by other intracellular or extracellular factors, but the mechanisms of these regulations are not yet well understood. It has been proposed that ENaC may be regulated by an associated ATP-binding cassette protein such as the cystic fibrosis conductance regulator or the K channel-associated sulfonylurea receptor. Glibenclamide, a known inhibitor of sulfonylurea receptor and cystic fibrosis conductance regulator, induced a dose-dependent and reversible stimulation (of the order of 40–50%) of the amiloride-sensitive current in oocytes expressingXenopus ENaC, with aK1/2 of 45 ± 5 μM. A similar effect was observed in oocytes expressing human ENaC, but not rat ENaC. Measurements performed with various combinations of rat andXenopus subunits indicated that several subunits are involved in this effect. Glibenclamide also increased the transepithelial Na transport by the A6 Xenopus kidney cell line. Single-channel current recordings showed a doubling of the number of the open channels when glibenclamide was applied locally to the extracellular surface of the cell membrane. These results support the hypothesis of the existence of an associated ATP-binding cassette-type regulatory protein associated with the epithelial sodium channel. The American Society for Pharmacology and Experimental Therapeutics