Inhibition of Na+/K+-ATPase by endothelin-1 in human nonpigmented ciliary epithelial cells

Ganesh Prasanna, Adnan Dibas, Christina Hulet, Thomas Yorio

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Endothelin-1 (ET-1), a potent vasoconstrictor, lowers intraocular pressure in mammals, either by enhancing the outflow of aqueous humor (AH) via the trabecular meshwork and Schlemm's canal or by reducing AH formation at the ciliary epithelium. Aqueous humor production occurs by passive diffusion of water coupled with active transport of ions, mainly involving Na+:K+:2Cl- cotransporter and Na+/K+-ATPase pump from serosal to aqueous side. Presently, we have evaluated the effects of ET-1 on Na+:K+:2Cl- cotransport and Na+/K+-ATPase activity in HNPE cells using 86Rb+ uptake. ET-1 (100 pM-100 nM) decreased mean 86Rb+ uptake by 15% during a 15-min uptake period. ET-1's effect was not prevented by BQ610, an ETA receptor antagonist, but was blocked by BQ788, an ETB receptor antagonist. ET-1's effect was mimicked by sarafotoxin, an ETB agonist. ET-1-induced reduction in 86Rb+ uptake was additive with bumetanide, a selective inhibitor of Na+:K+:2Cl- cotransporter but not with ouabain, a selective inhibitor of the Na+/K+-ATPase. ET-1 did not affect iberiotoxin-sensitive maxi K+ channels. This suggests that ET-1-induced reduction in 86Rb+ uptake is mediated through the inhibition of the Na+/K+-ATPase via an ETB-like receptor. These findings are consistent with an ET-1 effect on active ion transport activity in HNPE cells that could explain the reduction in aqueous humor production and the lowering of intraocular pressure.

Original languageEnglish
Pages (from-to)966-971
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - 14 Mar 2001

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