Functional pharmacological evidence for EP2 and EP4 prostanoid receptors in immortalized human trabecular meshwork and non-pigmented ciliary epithelial cells

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
J Y Crider, Najam A Sharif

Abstract

The aim of these studies was to characterize the molecular pharmacology of the prostanoid receptors positively coupled to stimulation of adenylyl cyclase activity in immortalized human trabecular meshwork (TM-3) cells and to compare these results with that of the receptors in immortalized human nonpigmented epithelial (NPE) cells. In general, the TM-3 and NPE cells showed a similar profile with respect to their responses to various prostaglandin (PG) receptor agonists. The rank order of potency (EC50; means +/- SEM) for these compounds in the TM-3 cells was: PGE2 (124 +/- 21 nM) > 13,14-dihydro-PGE1 (430 +/- 110 nM) = PGE1 (522 +/- 345 nM) > 11-deoxy-PGE1 (1063 +/- 118 nM) = 16,16-dimethyl-PGE2 (1776 +/- 460 nM) = butaprost (1920 +/- 527 nM) > PGD2 = PGI2 = PGF2alpha (n = 3 - 12). While the agonist profile indicated the presence of EP2 receptors, the effects of the EP4 receptor antagonists suggested the additional expression of EP4 receptors in both of these cells. Thus, the EP4 receptor antagonist, AH23848B, at a concentration of 30 microM, caused a dextral shift in the PGE2 concentration-response curves in both TM-3 and NPE cells coupled with a 20-28% decrease in the maximal response of PGE2, indicating apparent noncompetitiv...Continue Reading

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Citations

Feb 8, 2003·Experimental Eye Research·Jerry G WebbCraig E Crosson
May 1, 2004·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Toshihiko Matsuo
Mar 22, 2008·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Zaher A Radi, James A Render
Nov 19, 2013·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Najam A SharifDorette Ellis
Sep 20, 2005·Acta Physiologica Scandinavica·R LarsenN Bindslev
Oct 7, 2004·European Journal of Pharmacology·Richard J WilsonHeather Giles
Feb 3, 2005·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Naj A SharifTerry L Davis
Jan 13, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Najam A Sharif
Apr 22, 2018·British Journal of Pharmacology·Najam A Sharif, Peter G Klimko
Jul 11, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Masahiro FuwaJin-Zhong Zhang
Sep 17, 2004·Current Eye Research·Willem KamphuisPhilip F J Hoyng
Aug 30, 2019·Expert Opinion on Therapeutic Patents·Andrea Angeli, Claudiu T Supuran
Apr 14, 2016·Ophthalmic Genetics·Lance P Doucette, Michael A Walter

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