Inhibition of rho-associated kinase reduces MLC20 phosphorylation and contractility of intact myometrium and attenuates agonist-induced Ca2+ sensitization of force of permeabilized rat myometrium.
The role of rhoA/rho-associated kinase (ROK) signaling pathways in agonist-induced contraction of the rat myometrium was investigated. We measured the [Ca(2+)](i)-force relationship, phosphorylation of myosin regulatory light chains (MLC(20)) in intact tissue and the Ca(2+)-sensitization of force in permeabilized myometrial cells of rat. In measurements of the relationship between [Ca(2+)](i) and tension in intact tissue, Y-27632, a ROK inhibitor, significantly attenuated the carbachol-induced contraction without changing [Ca (2+)](i). Phosphorylation of MLC(20) was increased by carbachol and this increased phosphorylation was blocked by treatment of tissue with Y-27632. In tension measurements of single hyperpermeable cells, carbachol evoked sustained contraction at constant pCa 6.7 and these agonist-induced contractions were decreased by treatment with Y-27632. These results suggest that activation of a ROK-mediated signaling pathway(s) plays an important role in agonist-induced alterations in MLC(20) phosphorylation and force of rat myometrium.
Oh
Jae-Hwan
JH
Department of Surgery, Gachon Medical School, Gil Medical Center.
You
Sung-Kyung
SK
Hwang
Mi-Kyung
MK
Ahn
Duck-Sun
DS
Kwon
Seong-chun
SC
Taggart
Michael J
MJ
Lee
Young-Ho
YH
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D010539:Permeability; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*; D054460:rho-Associated Kinases
D000577:Amides; D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D009281:Naphthalenes; D011725:Pyridines; C061462:calphostin B; C108830:Y 27632; D002217:Carbachol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D002118:Calcium