Prostaglandin F2α but not latanoprost, increases the Ca2+ sensitivity of the pig iris sphincter muscle

Abstract

PURPOSE. To determine the mechanisms underlying prostaglandin (PG) F 2α-, carbachol (CCh)-, or latanoprost (a PGF2α 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 α-toxin. The effects of PGF2α 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, PGF2α and CCh, but not latanoprost, caused an additional tension development at a fixed intracellular Ca 2+ concentration ([Ca2+]i) and also shifted the [Ca2+]i-tension curve to the left, thus indicating that PGF2α and CCh, but not latanoprost, induced increases in Ca2+ sensitivity (Ca2+ sensitization). This Ca 2+ 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. PGF 2α increased the level of MLC phosphorylation at a constant [Ca2+]i. CONCLUSIONS. PGF2α, 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 PGF2α and was thought to play a beneficial role in glaucoma treatment. Copyright © Association for Research in Vision and Ophthalmology.