Prostaglandin F₂α, but Not Latanoprost, Increases the Ca²⁺Sensitivity of the Pig Iris Sphincter Muscle

PURPOSE: To determine the mechanisms underlying prostaglandin (PG) F(2)alpha-(,) carbachol (CCh)-, or latanoprost (a PGF(2)alpha analogue)-induced contraction of the pig iris sphincter muscle. METHODS: Effects of these agents on myofilament Ca(2+) sensitivity were evaluated and compared with the use of receptor-coupled permeabilized preparations by alpha-toxin. The effects of PGF(2)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, PGF(2)alpha and CCh, but not latanoprost, caused an additional tension development at a fixed intracellular Ca(2+) concentration ([Ca(2+)](i)) and also shifted the [Ca(2+)](i)-tension curve to the left, thus indicating that PGF(2)alpha and CCh, but not latanoprost, induced increases in Ca(2+) sensitivity (Ca(2+) 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(2)alpha increased the level of MLC phosphorylation at a constant [Ca(2+)](i). CONCLUSIONS: PGF(2)alpha, but not latanoprost, induced Ca(2+) 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 Ca(2+) sensitization mechanism was different from that of PGF(2)alpha and was thought to play a beneficial role in glaucoma treatment.