A ROLE FOR RHO-KINASE IN Ca2+-INDEPENDENT CONTRACTIONS INDUCED BY PHORBOL-12,13-DIBUTYRATE

被引:14
作者
Baek, Inji [1 ]
Jeon, Su Bun [1 ]
Kim, Juyoung [1 ]
Seok, Young Mi [1 ]
Song, Min-Ji [1 ]
Chae, Shung Chull [2 ,3 ]
Jun, Jae Eun [2 ,3 ]
Park, Wee Hyun [2 ,3 ]
Kim, In Kyeom [1 ,3 ]
机构
[1] Kyungpook Natl Univ, Sch Med, Dept Pharmacol, Taegu 700422, South Korea
[2] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Taegu 700422, South Korea
[3] Kyungpook Natl Univ, Sch Med, Cardiovasc Res Inst, Taegu 700422, South Korea
来源
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2009年 / 36卷 / 03期
关键词
Ca2+-independent contraction; CPI-17; GTP-RhoA; myosin phosphatase targeting subunit 1 (MYPT1); phorbol-12,13-dibutyrate; protein kinase C; Rho-kinase; ARTERIAL SMOOTH-MUSCLE; LIGHT-CHAIN PHOSPHORYLATION; PHOSPHATASE TARGET-SUBUNIT; DEPENDENT PROTEIN-KINASE; INTEGRIN-LINKED KINASE; MYOSIN-BINDING SUBUNIT; SIGNAL-TRANSDUCTION; CA2+ SENSITIZATION; CALCIUM; INHIBITION;
D O I
10.1111/j.1440-1681.2008.05045.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Phorbol-12,13-dibutyrate (PDBu) is an activator of protein kinase C (PKC) that causes contractions in both physiological salt solutions and Ca2+-depleted solutions. In the present study, we tested the hypothesis that Rho-kinase plays a role in Ca2+-independent contractions induced by PDBu in vascular smooth muscles. 2. In Ca2+-free solution, 0.1 and 1 mu mol/L PDBu induced contraction and myosin light chain (MLC20) phosphorylation, both of which were approximately 40% of responses obtained in normal Krebs' solution. Hydroxyfasudil (H1152; 1 mu mol/L), an inhibitor of Rho-kinase, but not ML7 (10 mmol/L), an inhibitor of myosin light chain kinase, inhibited Ca2+-independent contractions induced by PDBu. 3. In Ca2+-free solution, PDBu increased phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and CPI-17 (PKC-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa). This action was inhibited by H1152, with the phosphorylation of CPI-17 almost completely abolished by 1 mu mol/L Ro31-8220, an inhibitor of PKC. 4. In Ca2+-free solution, PDBu increased the amount of GTP-RhoA (an activated form of RhoA). This increase was blocked by the PKC inhibitor Ro31-8220, but not by the Rho kinase inhibitor H1152. 5. In conclusion, RhoA/Rho-kinase plays an important role in Ca2+-independent contractions induced by PDBu in vascular smooth muscles. The results of the present study suggest that PDBu induces Ca2+-independent contractions by inhibiting myosin light chain phospatase (MLCP) through activation of GTP-RhoA and subsequent phosphorylation of MYPT1 and CPI-17.
引用
收藏
页码:256 / 261
页数:6
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