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Abstract #15138 Published in IGR 8-4
Prostaglandin F2α, but not latanoprost, increases the Ca2+ sensitivity of the pig iris sphincter muscle
Hasegawa Y; Nishimura J; Niiro N; Hirano K; Ishibashi T; Kanaide HInvestigative Ophthalmology and Visual Science 2006; 47: 4865-4871
PURPOSE: To determine the mechanisms underlying prostaglandin (PG)F2 α-, carbachol (CCh)-, or latanoprost (a F2 α 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 F2 α 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, F2 α 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 F2 α 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. F2 α increased the level of MLC phosphorylation at a constant [Ca2+ ]i . CONCLUSIONS: F2 α, 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 F2 α and was thought to play a beneficial role in glaucoma treatment.
Dr. Y. Hasegawa, Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Classification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
11.4 Prostaglandins (Part of: 11 Medical treatment)
2.8 Iris (Part of: 2 Anatomical structures in glaucoma)
