JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kelly, C. R.
Right arrow Articles by Sharif, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kelly, C. R.
Right arrow Articles by Sharif, N. A.

Vol. 304, Issue 1, 238-245, January 2003

Real-Time Intracellular Ca2+ Mobilization by Travoprost Acid, Bimatoprost, Unoprostone, and Other Analogs via Endogenous Mouse, Rat, and Cloned Human FP Prostaglandin Receptors

Curtis R. Kelly, Gary W. Williams and Najam A. Sharif

Molecular Pharmacology Unit, Pharmaceutical Products Research, Alcon Research, Ltd., Fort Worth, Texas

The ability of a number of prostaglandin F2alpha (PGF2alpha ) analogs to mobilize intracellular Ca2+ [Ca2+]i and to compete for [3H]PGF2alpha binding to prostaglandin F2alpha receptors (FP) was evaluated. Radioligand binding studies measuring displacement of [3H]PGF2alpha by a variety of FP prostaglandin analogs yielded the following rank order of affinities: travoprost acid [(+)-16-m-trifluorophenoxy tetranor PGF2alpha ; (+)-fluprostenol] > bimatoprost acid (17-phenyl-trinor PGF2alpha ) unoprostone (13,14-dihydro-15-keto-20-ethyl PGF2alpha ) = bimatoprost (17-phenyl-trinor PGF2alpha ethyl amide) >=  Lumigan (bimatoprost ophthalmic solution). In FP functional studies, travoprost acid (EC50 = 17.5-37 nM, n = 13), bimatoprost acid (EC50 = 23.3-49.0 nM, n = 6-12), unoprostone (EC50 = 306-1270 nM, n = 4-8), bimatoprost (EC50 = 3070- 3940 nM, n = 4-9), and Lumigan (EC50 = 1470-3190 nM, n = 5-9) concentration dependently stimulated [Ca2+]i mobilization via the rat (A7r5 cells), mouse (3T3 cells), and cloned human ocular FP prostanoid receptors. The rank order of potency of these compounds at the FP receptor of the three species was similar and in good agreement with the determined binding affinities. The agonist effects of these compounds were concentration dependently blocked by the FP receptor-selective antagonist, AL-8810 (11beta -fluoro-15-epi-15-indanyl-tetranor PGF2alpha ) (Ki = 0.6-1.3 µM). These studies have demonstrated that bimatoprost, unoprostone, and bimatoprost acid possess direct agonist activities at the rat, mouse, and human FP prostanoid receptor and that travoprost acid is the most potent of the synthetic FP prostaglandin analogs tested.

0022-3565/03/3041-0238$07.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Br. J. Ophthalmol.Home page
C B Camras, N A Sharif, M B Wax, and J Stjernschantz
Bimatoprost, the prodrug of a prostaglandin analogue
Br. J. Ophthalmol., June 1, 2008; 92(6): 862 - 863.
[Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
L B Cantor
Author's reply
Br. J. Ophthalmol., June 1, 2008; 92(6): 863 - 864.
[Full Text] [PDF]

Home page
 IOVSHome page
R.-F. Wang, D. J. Gagliuso, T. W. Mittag, and S. M. Podos
Effect of 15-Keto Latanoprost on Intraocular Pressure and Aqueous Humor Dynamics in Monkey Eyes
Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4143 - 4147.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. R. Romano and M. D. Lograno
Evidence for the Involvement of Cannabinoid CB1 Receptors in the Bimatoprost-Induced Contractions on the Human Isolated Ciliary Muscle
Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3677 - 3682.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. A. Sharif, C. R. Kelly, and M. McLaughlin
Human Trabecular Meshwork Cells Express Functional Serotonin-2A (5HT2A) Receptors: Role in IOP Reduction.
Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4001 - 4010.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. R. Kelly and N. A. Sharif
Pharmacological Evidence for a Functional Serotonin-2B Receptor in a Human Uterine Smooth Muscle Cell Line
J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1254 - 1261.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. G. Crowston, J. D. Lindsey, C. A. Morris, L. Wheeler, F. A. Medeiros, and R. N. Weinreb
Effect of Bimatoprost on Intraocular Pressure in Prostaglandin FP Receptor Knockout Mice
Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4571 - 4577.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. L. Hebert, M. Carmosino, O. Saito, G. Yang, C. A. Jackson, Z. Qi, R. M. Breyer, C. Natarajan, A. N. Hata, Y. Zhang, et al.
Characterization of a Rabbit Kidney Prostaglandin F2{alpha} Receptor Exhibiting Gi-restricted Signaling That Inhibits Water Absorption in the Collecting Duct
J. Biol. Chem., October 14, 2005; 280(41): 35028 - 35037.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. S. Nirodi, B. C. Crews, K. R. Kozak, J. D. Morrow, and L. J. Marnett
The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells
PNAS, February 17, 2004; 101(7): 1840 - 1845.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics.