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

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.