Abstract
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 using86Rb+ 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 in86Rb+ 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.
Footnotes
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Send reprint requests to: Ganesh Prasanna, Ph.D., Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, TX 76107. E-mail: gprasann{at}molly.hsc.unt.edu
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This work was supported in part by grants from Texas Higher Education Coordinating Board (09768-008/018) and National Eye Institute/National Institutes of Health (EY11979).
- Abbreviations:
- ET-1
- endothelin-1
- AH
- aqueous humor
- IOP
- intraocular pressure
- HNPE
- human nonpigmented ciliary epithelial
- SV40
- simian virus 40
- IBTX
- iberiotoxin
- OUA
- ouabain
- BUMET
- bumetanide
- S6C
- sarafotoxin
- PL
- phospholipase
- Received June 26, 2000.
- Accepted October 30, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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