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The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens.
Invest Ophthalmol Vis Sci. 2001 Apr; 42(5):1018-23.IO

Abstract

PURPOSE

Endothelin (ET)-1 is known to inhibit active NaK transport by as much as 50% in kidney tubule and other tissues. The presence of low levels of ET-1 in aqueous humor combined with the potential for release of ET-1 from ciliary processes suggests that the lens could be exposed to ET-1 in vivo. In this study, experiments were conducted to examine the influence of ET-1 on active NaK transport in porcine lens.

METHODS

The rate of Na,K-adenosine triphosphatase (Na,K-ATPase) dependent potassium transport was determined by measurements of ouabain-sensitive potassium (86Rb) uptake by intact lenses. Lens sodium content was measured by atomic absorption spectrophotometry. Cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. Cytoplasmic calcium concentration in cultured porcine lens epithelium was measured by a fluorescence technique using fura-2.

RESULTS

In the presence of ET-1 (0.1 nM or higher concentration), the rate of ouabain-sensitive potassium (86Rb) uptake was diminished. The ET receptor antagonist PD145065 (2 microM) suppressed the inhibitory effect of ET-1 (100 nM) on 86Rb uptake. Sodium content was detectably increased in lenses exposed to ET-1 for 24 hours. Forskolin (1 microM) caused an eightfold increase of cAMP in the lens epithelium, but no increase of cAMP was detected in the epithelium of lenses treated with ET-1. Genistein (150 microM), an inhibitor of tyrosine kinases, abolished the inhibitory effects of ET-1 on lens 86Rb uptake. ET-1 caused an increase of cytoplasmic calcium concentration in cultured porcine lens epithelium. The cytoplasmic calcium response to ET-1 was inhibited by PD145065 and genistein.

CONCLUSIONS

The results of the present study suggest that ET-1 causes inhibition of lens active Na-K transport by a mechanism that involves activation of ET receptors. Activation of ET receptors also causes an increase of cytoplasmic calcium concentration in cultured lens epithelial cells. Both responses to ET-1 appear to have a tyrosine kinase step, because they could be prevented by genistein. The physiological purpose of an ET-1-induced reduction in the rate of active Na-K transport by the lens is unknown at this time.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky 40202, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11274080

Citation

Okafor, M C., and N A. Delamere. "The Inhibitory Influence of Endothelin On Active Sodium-potassium Transport in Porcine Lens." Investigative Ophthalmology & Visual Science, vol. 42, no. 5, 2001, pp. 1018-23.
Okafor MC, Delamere NA. The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens. Invest Ophthalmol Vis Sci. 2001;42(5):1018-23.
Okafor, M. C., & Delamere, N. A. (2001). The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens. Investigative Ophthalmology & Visual Science, 42(5), 1018-23.
Okafor MC, Delamere NA. The Inhibitory Influence of Endothelin On Active Sodium-potassium Transport in Porcine Lens. Invest Ophthalmol Vis Sci. 2001;42(5):1018-23. PubMed PMID: 11274080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The inhibitory influence of endothelin on active sodium-potassium transport in porcine lens. AU - Okafor,M C, AU - Delamere,N A, PY - 2001/3/29/pubmed PY - 2001/5/18/medline PY - 2001/3/29/entrez SP - 1018 EP - 23 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 42 IS - 5 N2 - PURPOSE: Endothelin (ET)-1 is known to inhibit active NaK transport by as much as 50% in kidney tubule and other tissues. The presence of low levels of ET-1 in aqueous humor combined with the potential for release of ET-1 from ciliary processes suggests that the lens could be exposed to ET-1 in vivo. In this study, experiments were conducted to examine the influence of ET-1 on active NaK transport in porcine lens. METHODS: The rate of Na,K-adenosine triphosphatase (Na,K-ATPase) dependent potassium transport was determined by measurements of ouabain-sensitive potassium (86Rb) uptake by intact lenses. Lens sodium content was measured by atomic absorption spectrophotometry. Cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. Cytoplasmic calcium concentration in cultured porcine lens epithelium was measured by a fluorescence technique using fura-2. RESULTS: In the presence of ET-1 (0.1 nM or higher concentration), the rate of ouabain-sensitive potassium (86Rb) uptake was diminished. The ET receptor antagonist PD145065 (2 microM) suppressed the inhibitory effect of ET-1 (100 nM) on 86Rb uptake. Sodium content was detectably increased in lenses exposed to ET-1 for 24 hours. Forskolin (1 microM) caused an eightfold increase of cAMP in the lens epithelium, but no increase of cAMP was detected in the epithelium of lenses treated with ET-1. Genistein (150 microM), an inhibitor of tyrosine kinases, abolished the inhibitory effects of ET-1 on lens 86Rb uptake. ET-1 caused an increase of cytoplasmic calcium concentration in cultured porcine lens epithelium. The cytoplasmic calcium response to ET-1 was inhibited by PD145065 and genistein. CONCLUSIONS: The results of the present study suggest that ET-1 causes inhibition of lens active Na-K transport by a mechanism that involves activation of ET receptors. Activation of ET receptors also causes an increase of cytoplasmic calcium concentration in cultured lens epithelial cells. Both responses to ET-1 appear to have a tyrosine kinase step, because they could be prevented by genistein. The physiological purpose of an ET-1-induced reduction in the rate of active Na-K transport by the lens is unknown at this time. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/11274080/The_inhibitory_influence_of_endothelin_on_active_sodium_potassium_transport_in_porcine_lens_ L2 - https://iovs.arvojournals.org/article.aspx?volume=42&issue=5&page=1018 DB - PRIME DP - Unbound Medicine ER -