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

Abstract

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.

Induction by Latanoprost of Collagen Gel Contraction Mediated by Human Tenon Fibroblasts: Role of Intracellular Signaling Molecules

“…Prostaglandin F 2␣ , but not latanoprost, was found to increase the Ca 2ϩ sensitivity of the pig iris sphincter muscle in an MLC phosphorylation-dependent manner. 35 The lack of apparent effect of latanoprost on MLC phosphorylation in HTFs in the present study suggests that MLC phosphorylation-independent Ca 2ϩ sensitization may underlie the latanoprost-induced contraction of these cells. However, we found that ML-7 (a selective inhibitor of MLC kinase) prevented HTF-mediated collagen gel contraction regardless of the absence or presence of latanoprost, suggesting that MLC phosphorylation is necessary for both basal and stimulated HTF contraction.…”

Prostamides (prostaglandin‐ethanolamides) and their pharmacology

“…This corresponds to the low bimatoprost conversion rates observed in isolated bovine and human ocular tissues ( Maxey et al , 2002 ; Davies et al , 2003 ; Krauss and Woodward, 2004 ). Even the ester latanoprost undergoes low enzymatic hydrolysis in certain tissues, as indicated by the very weak activity of latanoprost in the isolated feline ( Resul et al , 1997 ) or porcine iris ( Hasegawa et al , 2006 ). Finally, potent stimulation of the isolated rabbit uterus was attributed to the activity of intact bimatoprost, since bioassay indicated no enzymatic hydrolysis to the free acid metabolite ( Chen et al , 2005 ).…”

Rho-Kinase, but not Protein Kinase C, is Involved in Generation of the Spontaneous Tone in the Resting Phase of the Isolated Pig Iris Sphincter Muscle

“…5−7,17,21 Hasegawa et al 17 reported that, in isolated α-toxin-permeabilized pig iris sphincter muscle, Y27632, a Rho-kinase inhibitor, inhibited the carbachol-induced enhancement of contraction at a fixed concentration of intracellular free Ca 2+ [Ca 2+ ] i . Carbachol stimulates the M3 muscarinic receptor coupled to a heterotrimetric GTPbinding protein (Gq).…”

“…The present findings suggest that PKC is not involved in the generation of spontaneous tone in the resting phase. Hasegawa et al 17 observed that, in the α-toxin-permeabilized pig iris sphincter muscle, Gq-coupled receptor-mediated Ca 2+ sensitization was inhibited by Y27632 but not by GF109203X. Furthermore, they also observed that PDBu, an activator of PKC, had no effect on the resting tension in the intact and α-toxin-permeabilized pig iris sphincter muscle and that CPI-17 expression was under detectable levels by immunoblot analysis in this tissue.…”

“…In a recent study, it was reported that Rho-kinase, but not PKC, plays an important role in the contraction mediated by Gq-coupled receptor of the α-toxin-permeabilized pig iris sphincter muscle. 17 However, the role of Rho-kinase and/or PKC on the resting tension in the absence of any stimulus has not yet been determined. The purpose of the present study was to clarify the role of Rho-kinase and/or PKC in the resting tension of the isolated pig iris sphincter muscle.…”