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(10)

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Abstract #12279 Published in IGR 7-2

Ocular hypotensive DP-class prostaglandin receptor affinities determined by quantitative autoradiography on human eye sections

Sharif NA; Davis TL; Williams GW
Journal of Ocular Pharmacology and Therapeutics 2005; 21: 121-132

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The aim of this study was to define the localization and pharmacology of DP-prostaglandin receptors in human eye sections using a novel DP-antagonist radioligand ([³ H]-BWA868C), using various intraocular pressure (IOP)-lowering DP-prostaglandins and the technique of quantitative autoradiography on 20-μm sections of frozen human eyes. [³ H] BWA868C yielded well-defined autoradiograms of DP-receptors in human eyes with up to 82% specific binding. High densities of DP-receptors were associated with the ciliary epithelium/process, iris, choroid, longitudinal and circular ciliary muscles, and retina. Low specific binding was observed in the lens and cornea. The DP-receptor agonists, BW245C (K_i = 4-8 nM), SQ27986 (K_i = 6-9 nM), ZK118182 (K_i = 12-33 nM), 3,4-dihydro-ZK118182 (AL-6556; K_i = 1.6-4.3 (μM) and 3,4-dihydro-ZK118182 isopropyl ester (AL-6598; K_i = 2.9-9.7 μM), exhibited varying affinities for human DP-receptors in the ciliary process, longitudinal and circular ciliary muscles, and iris, respectively. These human ocular tissue affinity values correlated well with nonocular tissue affinities and functional potencies of these prostaglandins in cultured cells (r = 0.93-0.99). In conclusion, these quantitative autoradiographic studies revealed a high density of DP-prostaglandin receptors in human ciliary muscles, ciliary process, and iris, indicating that this class of prostaglandin may lower IOP by uveoscleral pathway and also by inhibiting aqueous humor production. The pharmacological attributes of [³ H]BWA868C-labeled receptor sites studied using in situ quantitative autoradiography matched those previously documented for several other DP-receptor-containing cells and tissues.

Dr. N.A. Sharif, Molecular Pharmacology Unit (R2-19), Alcon Research Ltd., 6201 South Freeway, Fort Worth, TX 76134-2099, USA

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Classification:

11.4 Prostaglandins (Part of: 11 Medical treatment)

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