Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit.

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Yamamura H, Ugawa S, Ueda T, Shimada S

Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit.

J Pharmacol Exp Ther. 2005 Nov;315(2):965-9. Epub 2005 Aug 17.

PubMed ID

16107516 [ View in PubMed

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Abstract

The epithelial Na(+) channel (ENaC) regulates Na(+) homeostasis in cells and across epithelia. Four homologous ENaC subunits (alpha, beta, gamma, and delta) have been isolated in mammals. Combination of alpha-, beta-, and gamma-subunits or delta-, beta-, and gamma-subunits forms fully functional channels. Amiloride is a well known blocker of the ENaC family that inhibits both channel complexes. However, no specific antagonists are currently known that distinguish them. Here, we show that Evans blue, a diagnostic aid for the measurement of blood volume and vascular permeability, inhibits the activity of the delta-subunit expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in human ENaCdeltabetagamma-expressing oocytes were inhibited by the application of Evans blue in a concentration-dependent manner with an IC(50) value of 143 muM. Evans blue markedly inhibited the delta-subunit current but did not block the alpha-subunit current. In conclusion, Evans blue is the first known delta-subunit-specific antagonist of ENaC. This finding provides us with a key compound for elucidating the physiological and pathological functions of ENaCdelta in humans and for drug development in the ENaC family.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amiloride	Amiloride-sensitive sodium channel subunit delta	Protein	Humans	Yes	Inhibitor	Details