The goal of this project is to understand the roles of the a2-adrenergic and prostaglandin EP receptor subtypes in the pharmacology and physiology of aqueous secretion by the mammalian ocular ciliary epithelium. Towards this end the PI will continue the work that he has started to identify the cellular and subcellular localization of the a2-adrenergic receptor subtypes in the ciliary epithelium using immunofluorescence microscopy. He will also develop antibodies to the prostaglandin EP receptor subtypes and use these in conjunction with the polymerase chain reaction for the localization of prostaglandin receptors in the ciliary epithelium. Of particular interest is the possible interaction of the a2-adrenergic and prostaglandin receptors with the functional activity of proteins that are involved with secretion, such as the Na+/K+/2C1- co-transporter and the aquaporins or water channels. In this regard, the PI has very exciting preliminary data which shows that forskolin, a modulator of intracellular cAMP, can stimulate the water permeability of aquaporin-1 and can activate a novel cationic conductance by the water channel. This suggests that receptors which can modulate intracellular cAMP formation, such as the a2-adrenergic and prostaglandin EP, can potentially regulate the activity of aquaporin-1. In fact, following heterologous expression of aquaporin-1 and prostaglandin EP2 receptors in Xenopus oocytes we can show PGE2-activation of a cationic conductance by aquaporin-1. These studies will contribute to our understanding of the regulation of aqueous secretion in the ciliary epithelium and could be potentially very important towards our understanding of the pathophysiology and treatment of glaucoma.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
Schools of Pharmacy
United States
Zip Code
Ji, R; Sanchez, C M; Chou, C L et al. (2012) Prostanoid EP? receptors mediate up-regulation of the orphan nuclear receptor Nurr1 by cAMP-independent activation of protein kinase A, CREB and NF-?B. Br J Pharmacol 166:1033-46
Ji, Ruyue; Chou, Chih-Ling; Xu, Wei et al. (2010) EP1 prostanoid receptor coupling to G i/o up-regulates the expression of hypoxia-inducible factor-1 alpha through activation of a phosphoinositide-3 kinase signaling pathway. Mol Pharmacol 77:1025-36
Hutchinson, Anthony J; Coons, Serena C; Chou, Chih-Ling et al. (2010) Induction of angiogenic immediate early genes by activation of FP prostanoid receptors in cultured human ciliary smooth muscle cells. Curr Eye Res 35:408-18
Xu, Wei; Chou, Chih-Ling; Israel, Davelene D et al. (2009) PGF(2alpha) stimulates FP prostanoid receptor mediated crosstalk between Ras/Raf signaling and Tcf transcriptional activation. Biochem Biophys Res Commun 381:625-9
Hutchinson, Anthony J; Chou, Chih-Ling; Israel, Davelene D et al. (2009) Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF. Neurochem Int 54:439-46
Israel, Davelene D; Regan, John W (2009) EP(3) prostanoid receptor isoforms utilize distinct mechanisms to regulate ERK 1/2 activation. Biochim Biophys Acta 1791:238-45
Taniguchi, Tomoko; Fujino, Hiromichi; Israel, Davelene D et al. (2008) Human EP3(I) prostanoid receptor induces VEGF and VEGF receptor-1 mRNA expression. Biochem Biophys Res Commun 377:1173-8
Xu, Wei; Chou, Chih-Ling; Sun, Haipeng et al. (2008) FP prostanoid receptor-mediated induction of the expression of early growth response factor-1 by activation of a Ras/Raf/mitogen-activated protein kinase signaling cascade. Mol Pharmacol 73:111-8
Fujino, Hiromichi; Chen, Xiao-bo; Regan, John W et al. (2007) Indomethacin decreases EP2 prostanoid receptor expression in colon cancer cells. Biochem Biophys Res Commun 359:568-73
Chen, X-B; Regan, J W (2006) Activation of the human FP prostanoid receptor disrupts mitosis progression and generates aneuploidy and polyploidy. Cell Mol Life Sci 63:112-21

Showing the most recent 10 out of 29 publications