Prostaglandin F2alpha, but not latanoprost, increases the Ca2+ sensitivity of the pig iris sphincter muscle.
OBJECTIVE
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.
Hasegawa
Yuhei
Y
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.
Nishimura
Junji
J
Niiro
Naohisa
N
Hirano
Katsuya
K
Ishibashi
Tatsuro
T
Kanaide
Hideo
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D000077338:Latanoprost; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D013552:Swine; D010738:Type C Phospholipases / Q000494:pharmacology; D054460:rho-Associated Kinases
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D002217:Carbachol; D015237:Dinoprost; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D010738:Type C Phospholipases; D002118:Calcium