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(Investigative Ophthalmology and Visual Science. 2006;47:4865-4871.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1518
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Prostaglandin F2{alpha}, but Not Latanoprost, Increases the Ca2+ Sensitivity of the Pig Iris Sphincter Muscle

Yuhei Hasegawa,1,2 Junji Nishimura,1 Naohisa Niiro,1 Katsuya Hirano,1 Tatsuro Ishibashi,2 and Hideo Kanaide1,3

1From the Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, the 2Department of Ophthalmology, Graduate School of Medical Sciences, and the 3Kyushu University COE Program on Lifestyle-Related Diseases, Kyushu University, Fukuoka, Japan.

PURPOSE. To determine the mechanisms underlying prostaglandin (PG) F2{alpha}-, carbachol (CCh)-, or latanoprost (a PGF2{alpha} analogue)-induced contraction of the pig iris sphincter muscle.

METHODS. Effects of these agents on myofilament Ca2+ sensitivity were evaluated and compared with the use of receptor-coupled permeabilized preparations by {alpha}-toxin. The effects of PGF2{alpha} and CCh on the phosphorylation of myosin light chain (MLC) were also analyzed.

RESULTS. In the intact strips, all three of these agents induced contractions. In permeabilized strips, PGF2{alpha} and CCh, but not latanoprost, caused an additional tension development at a fixed intracellular Ca2+ concentration ([Ca2+]i) and also shifted the [Ca2+]i-tension curve to the left, thus indicating that PGF2{alpha} and CCh, but not latanoprost, induced increases in Ca2+ sensitivity (Ca2+ sensitization). This Ca2+ sensitization could have been inhibited by Y27632, a rho kinase inhibitor, but not by GF109203X, a protein kinase C (PKC) inhibitor or by PD98059, a mitogen-activated protein (MAP) kinase inhibitor. PGF2{alpha} increased the level of MLC phosphorylation at a constant [Ca2+]i.

CONCLUSIONS. PGF2{alpha}, but not latanoprost, induced Ca2+ sensitization of the pig iris sphincter muscle in an MLC phosphorylation–dependent manner through the rho–rho kinase pathway. The effect of latanoprost on the Ca2+ sensitization mechanism was different from that of PGF2{alpha} and was thought to play a beneficial role in glaucoma treatment.




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Y. Liu, J.-A. Ko, R. Yanai, K. Kimura, T.-i. Chikama, T. Sagara, and T. Nishida
Induction by Latanoprost of Collagen Gel Contraction Mediated by Human Tenon Fibroblasts: Role of Intracellular Signaling Molecules
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1429 - 1436.
[Abstract] [Full Text] [PDF]


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