PMID: 9185033Jun 1, 1997Paper

High affinity binding sites for 12(R)-Hydroxyeicosatrienoic acid [12(R)-HETrE] in microvessel endothelial cells

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
R A Stoltz, M L Schwartzman

Abstract

12(R)-HETrE is an NADPH-dependent arachidonic acid-derived metabolite whose synthesis is induced several fold in inflamed corneal epithelium correlating with the development of the in situ inflammatory response, i.e., vasodilation, PMN chemotaxis, endothelial cell mitogenesis, and neovascularization. Because this novel eicosanoid may serve as an endogenous mediator of the angiogenic response in the cornea during inflammation we probed microvessel endothelial cells for a specific binding site which could possibly account for the mechanism by which this eicosanoid initiates changes in cellular activity. Binding of radioactive ligand [3H-12(R)-HETrE] was saturable with time and concentration. Scatchard analysis indicated a single, saturable binding site for 12(R)-HETrE with a Bmax = 24,700 sites/cell and an apparent Kd = 0.043 nM. Thin layer chromatography analysis of cell-associated ligand revealed that esterification of 12(R)-HETrE was 2-7 fold less than unesterified, cell bound ligand. The concentrations of 12(R)-HETrE at which maximum biological activity has been observed, i.e., 0.1 nM, roughly corresponds to the Kd value, suggesting a functional link to this binding site. These studies begin to reveal a potential mechanism by...Continue Reading

References

Mar 11, 1991·Trends in Neurosciences·R W OrdwayJ V Walsh
Apr 1, 1991·Experimental Eye Research·J L MasferrerM Laniado-Schwartzman
Jan 1, 1989·Annual Review of Pharmacology and Toxicology·P V HalushkaT A Morinelli
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Feb 1, 1993·The Journal of Clinical Investigation·T SatohA I Katz

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Citations

May 2, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jian-Kang ChenRaymond C Harris
Jul 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Alexandre MezentsevMichal Laniado-Schwartzman
Sep 20, 2005·The Journal of Pharmacology and Experimental Therapeutics·Liping DuDiane S Keeney
Mar 20, 2002·The Journal of Biological Chemistry·Alexander MezentsevMichal Laniado-Schwartzman
May 14, 2009·Seminars in Ophthalmology·Pauline LimUla V Jurkunas

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