scholarly journals Leukotriene C4 enhances the contraction of porcine tracheal smooth muscle through the activation of Y-27632, a rho kinase inhibitor, sensitive pathway

2001 ◽  
Vol 132 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Hidekazu Setoguchi ◽  
Junji Nishimura ◽  
Katsuya Hirano ◽  
Shosuke Takahashi ◽  
Hideo Kanaide
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Tracheal Smooth Muscle ◽  
Leukotriene C4 ◽  
Rho Kinase Inhibitor

Abstract 641: Expression Of GLUT4 In Vascular Smooth Muscle Affects Endothelial Function In Hypertension.

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kevin B Atkins ◽  
Jharna Saha ◽  
Frank C Brosius
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Interesting Phenomenon ◽  
Glut4 Expression ◽  
Endothelial Denudation ◽  
Rho Kinase Inhibitor ◽  
Total Body ◽  
Rats And Mice

Expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice, and total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity. To demonstrate that the effect on vascular response to GLUT4 overexpression is vascular rather than systemic in origin we utilized smooth muscle-specific GLUT4 transgenic mice (SMG4). GLUT4 expression in aortae of SMG4 compared to WT mice was increased 2-3 fold. Adult wild-type (WT) and SMG4 mice were made hypertensive or not through implantation of angiotensin II (AngII; 1.4mg/kg/d for 2 wks) or vehicle containing osmotic mini-pumps. Both WT and SMG4 mice AngII-treated mice exhibited significantly increased systolic blood pressure. In AngII-treated WT mice (WT-AngII) aortic GLUT4 expression was significantly decreased, whereas GLUT4 expression in aortae of AngII-treated SMG4 mice (SMG4-AngII) was maintained. The phosphorylation of ERM and MYPT1(Thr850) were significantly increased in aortae of WT-AngII compared to WT-Sham and SMG4-AngII mice. Responsiveness to the contractile agonists, phenylephrine, 5-HT, and PGF 2 was significantly increased in endothelium-intact aortic rings from WT-AngII mice, but remained normal in aortae of SMG4-AngII mice. Following pretreatment with Rho-kinase inhibitor Y-27632, relative inhibition of contractility to 5-HT was equal in aortae from WT-AngII and SMG4-AngII-treated mice. With endothelial denudation, contractility to 5-HT was equally enhanced in aortae of WT-AngII and SMG4-AngII-treated mice. Interestingly, whereas acetylcholine stimulated relaxation was significantly decreased in aortic rings of WT-AngII mice, relaxation in rings from SMG4-AngII mice was not significantly different from WT or SMG4. These results demonstrate an interesting phenomenon whereby decreased expression of GLUT4 in vascular smooth muscle leads to an endothelial dysfunction that not only impairs relaxation, but also enhances contractility.

Role of Rho in Ca2+-insensitive contraction and paxillin tyrosine phosphorylation in smooth muscle

2000 ◽  
Vol 279 (2) ◽  
pp. C308-C318 ◽  
Author(s):  
Dolly Mehta ◽  
Dale D. Tang ◽  
Ming-Fang Wu ◽  
Simon Atkinson ◽  
Susan J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Phosphorylation ◽  
Actin Polymerization ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Cytochalasin D ◽  
Cytoskeletal Proteins ◽  
Tracheal Smooth Muscle ◽  
Contractile Activation ◽  
Mlc Phosphorylation

We investigated whether Rho activation is required for Ca2+-insensitive paxillin phosphorylation, myosin light chain (MLC) phosphorylation, and contraction in tracheal muscle. Tyrosine-phosphorylated proteins have been implicated in the Ca2+-insensitive contractile activation of smooth muscle tissues. The contractile activation of tracheal smooth muscle increases tyrosine phosphorylation of the cytoskeletal proteins paxillin and focal adhesion kinase. Paxillin is implicated in integrin-mediated signal transduction pathways that regulate cytoskeletal organization and cell motility. In fibroblasts and other nonmuscle cells, paxillin tyrosine phosphorylation depends on the activation of Rho and is inhibited by cytochalasin, an inhibitor of actin polymerization. In permeabilized muscle strips, we found that ACh induced Ca2+-insensitive contraction, MLC phosphorylation, and paxillin tyrosine phosphorylation. Ca2+-insensitive contraction and MLC phosphorylation induced by ACh were inhibited by C3 transferase, an inhibitor of Rho activation; however, C3 transferase did not inhibit paxillin tyrosine phosphorylation. Ca2+-insensitive paxillin tyrosine phosphorylation was also not inhibited by the Rho kinase inhibitor Y-27632, by cytochalasin D, or by the inhibition of MLC phosphorylation. We conclude that, in tracheal smooth muscle, Rho mediates Ca2+-insensitive contraction and MLC phosphorylation but that Rho is not required for Ca2+-insensitive paxillin tyrosine phosphorylation. Paxillin phosphorylation also does not require actomyosin activation, nor is it inhibited by the actin filament capping agent cytochalasin D.

scholarly journals Resveratrol’s Impact on Vascular Smooth Muscle Cells Hyporeactivity: The Role of Rho-Kinase Inhibition

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Michał Wiciński ◽  
Bartosz Malinowski ◽  
Paweł Rajewski ◽  
Paweł Szychta ◽  
Eryk Wódkiewicz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinases ◽  
Vascular Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Pressure Effects ◽  
Kinase Inhibition ◽  
Rho Kinase Inhibitor ◽  
Dependent Protein

Resveratrol (3,5,4′-trihydroxystilbene) is a chemical compound belonging to the group of polyphenols and flavonoids. The aim of the present study was to determine the influence of resveratrol application along with certain modulating factors, such as 8Br-cGMP-activator of cGMP-dependent protein kinases, HA-1077-Rho-kinase inhibitor, and Bay K8644-calcium channel agonist, on VMSCs constriction triggered by phenylephrine. Resveratrol at a dose of 10 mg/kg/24 h administered for 4 weeks reduced the reactivity of the arteries to the pressure action of catecholamines. Tests performed after four weeks of resveratrol administration showed that 8Br-cGMP at the concentrations of 0.01 mM/l and 0.1 mM/l intensifies this effect. Simultaneous resveratrol and Bay K8644 administration led to a significant decrease in contractility compared to the vessels collected from animals (Res−). This effect was dependent on the concentration of Bay K8644. Resveratrol seems to be counteractive against Bay K8644 by blocking L-type calcium channels. As the concentration of HA-1077 increased, there was a marked hyporeactivity of the vessels to the pressure effects of phenylephrine. The results indicate synergy between resveratrol and Rho-kinase inhibition.

Animal model for angiotensin II effects in the internal anal sphincter smooth muscle: mechanism of action

2002 ◽  
Vol 282 (3) ◽  
pp. G461-G469 ◽  
Author(s):  
Ya-Ping Fan ◽  
Rajinder N. Puri ◽  
Satish Rattan
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Ang Ii ◽  
Kinase C ◽  
Rho Kinase Inhibitor ◽  
Isolated Smooth Muscle Cells

Effect of ANG II was investigated in in vitro smooth muscle strips and in isolated smooth muscle cells (SMC). Among different species, rat internal and sphincter (IAS) smooth muscle showed significant and reproducible contraction that remained unmodified by different neurohumoral inhibitors. The AT1antagonist losartan but not AT2 antagonist PD-123319 antagonized ANG II-induced contraction of the IAS smooth muscle and SMC. ANG II-induced contraction of rat IAS smooth muscle and SMC was attenuated by tyrosine kinase inhibitors genistein and tyrphostin, protein kinase C (PKC) inhibitor H-7, Ca2+ channel blocker nicardipine, Rho kinase inhibitor Y-27632 or p44/42mitogen-activating protein kinase (MAPK44/42) inhibitor PD-98059. Combinations of nicardipine and H-7, Y-27632, and PD-98059 caused further attenuation of the ANG II effects. Western blot analyses revealed the presence of both AT1 and AT2receptors. We conclude that ANG II causes contraction of rat IAS smooth muscle by the activation of AT1 receptors at the SMC and involves multiple intracellular pathways, influx of Ca2+, and activation of PKC, Rho kinase, and MAPK44/42.

1321: Y -27632, A RHO-Kinase Inhibitor, Inhibits Proliferation and Adrenergic Contraction of Prostatic Smooth Muscle

2004 ◽  
Vol 171 (4S) ◽  
pp. 348-348
Author(s):  
Rowland W. Rees ◽  
Neale A. Foxwell ◽  
David J. Ralph ◽  
Phil D. Kell ◽  
Salvador Moncada ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor

scholarly journals Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells

2000 ◽  
Vol 278 (1) ◽  
pp. C57-C65 ◽  
Author(s):  
Hiromitsu Nagumo ◽  
Yasuharu Sasaki ◽  
Yoshitaka Ono ◽  
Hiroyuki Okamoto ◽  
Minoru Seto ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Phosphatase Activity ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Myosin Phosphatase ◽  
Rho Kinase Inhibitor

In smooth muscle, a Rho-regulated system of myosin phosphatase exists; however, it has yet to be established whether Rho kinase, one of the downstream effectors of Rho, mediates the regulation of myosin phosphatase activity in vivo. In the present study, we demonstrate in permeabilized vascular smooth muscle cells (SMCs) that the vasodilator 1-(5-isoquinolinesulfonyl)-homopiperazine (HA-1077), which we show to be a potent inhibitor of Rho kinase, dose dependently inhibits Rho-mediated enhancement of Ca2+-induced 20-kDa myosin light chain (MLC20) phosphorylation due to abrogating Rho-mediated inhibition of MLC20dephosphorylation. By an immune complex phosphatase assay, we found that guanosine 5′- O-(3-thiotriphosphate) (GTPγS) stimulation of permeabilized SMCs caused a decrease in myosin phosphatase activity with an increase in the extent of phosphorylation of the 130-kDa myosin-binding regulatory subunit (MBS) of myosin phosphatase in a Rho-dependent manner. HA-1077 abolished both of the Rho-mediated events. Moreover, we observed that the pleckstrin homology/cystein-rich domain protein of Rho kinase, a dominant negative inhibitor of Rho kinase, inhibited GTPγS-induced phosphorylation of MBS. These results provide direct in vivo evidence that Rho kinase mediates inhibition of myosin phosphatase activity with resultant enhancement of MLC20phosphorylation in smooth muscle and reveal the usefulness of HA-1077 as a Rho kinase inhibitor.

The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPγS-, and phorbol ester-induced Ca2+ -sensitization of smooth muscle

FEBS Letters ◽  
1998 ◽  
Vol 440 (1-2) ◽  
pp. 183-187 ◽  
Author(s):  
Xiaohong Fu ◽  
Ming Cui Gong ◽  
Taiping Jia ◽  
Avril V Somlyo ◽  
Andrew P Somlyo
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Phorbol Ester ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor

scholarly journals Prostaglandin D2 Induces Ca2+ Sensitization of Contraction without Affecting Cytosolic Ca2+ Level in Bronchial Smooth Muscle

2018 ◽  
Vol 19 (10) ◽  
pp. 3036 ◽  
Author(s):  
Wataru Suto ◽  
Yusuke Ando ◽  
Takahiro Hirabayashi ◽  
Fumiko Takenoya ◽  
Seiji Shioda ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Active Form ◽  
Smooth Muscles ◽  
Rho Kinase ◽  
Allergic Airway Inflammation ◽  
Prostaglandin D2 ◽  
Smooth Muscle Contractility ◽  
High K ◽  
Rho Kinase Inhibitor

Prostaglandin D2 (PGD2) is one of the key lipid mediators of allergic airway inflammation, including bronchial asthma. However, the role of PGD2 in the pathogenesis of asthma is not fully understood. In the present study, the effect of PGD2 on smooth muscle contractility of the airways was determined to elucidate its role in the development of airway hyperresponsiveness (AHR). In isolated bronchial smooth muscles (BSMs) of naive mice, application of PGD2 (10−9–10−5 M) had no effect on the baseline tension. However, when the tissues were precontracted partially with 30 mM K+ (in the presence of 10−6 M atropine), PGD2 markedly augmented the contraction induced by the high K+ depolarization. The PGD2-induced augmentation of contraction was significantly inhibited both by 10−6 M laropiprant (a selective DP1 antagonist) and 10−7 M Y-27632 (a Rho-kinase inhibitor), indicating that a DP1 receptor-mediated activation of Rho-kinase is involved in the PGD2-induced BSM hyperresponsiveness. Indeed, the GTP-RhoA pull-down assay revealed an increase in active form of RhoA in the PGD2-treated mouse BSMs. On the other hand, in the high K+-depolarized cultured human BSM cells, PGD2 caused no further increase in cytosolic Ca2+ concentration. These findings suggest that PGD2 causes RhoA/Rho-kinase-mediated Ca2+ sensitization of BSM contraction to augment its contractility. Increased PGD2 level in the airways might be a cause of the AHR in asthma.

Distinctive G protein-dependent signaling in smooth muscle by sphingosine 1-phosphate receptors S1P1and S1P2

2004 ◽  
Vol 286 (5) ◽  
pp. C1130-C1138 ◽  
Author(s):  
Huiping Zhou ◽  
Karnam S. Murthy
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Muscle Cells ◽  
Rt Pcr ◽  
Sustained Contraction ◽  
Gastric Smooth Muscle ◽  
Rho Kinase Inhibitor ◽  
Sphingosine 1 Phosphate

We examined expression of sphingosine 1-phosphate (S1P) receptors and sphingosine kinase (SPK) in gastric smooth muscle cells and characterized signaling pathways mediating S1P-induced 20-kDa myosin light chain (MLC20) phosphorylation and contraction. RT-PCR demonstrated expression of SPK1 and SPK2 and S1P1and S1P2receptors. S1P activated Gq, G13, and all Giisoforms and stimulated PLC-β1, PLC-β3, and Rho kinase activities. PLC-β activity was partially inhibited by pertussis toxin (PTX), Gβ or Gαqantibody, PLC-β1 or PLC-β3 antibody, and by expression of Gαqor Gαiminigene, and was abolished by a combination of antibodies or minigenes. S1P-stimulated Rho kinase activity was partially inhibited by expression of Gα13or Gαqminigene and abolished by expression of both. S1P stimulated Ca2+release that was inhibited by U-73122 and heparin and induced concentration-dependent contraction of smooth muscle cells (EC501 nM). Initial contraction and MLC20phosphorylation were abolished by U-73122 and MLC kinase (MLCK) inhibitor ML-9. Initial contraction was also partially inhibited by PTX and Gαqor Gβ antibody and abolished by a combination of both antibodies. In contrast, sustained contraction and MLC20phosphorylation were partially inhibited by a PKC or Rho kinase inhibitor (bisindolylmaleimide and Y-27632) and abolished by a combination of both inhibitors but not affected by U-73122 or ML-9. These results indicate that S1P induces 1) initial contraction mediated by S1P2and S1P1involving concurrent activation of PLC-β1 and PLC-β3 via Gαqand Gβγi, respectively, resulting in inositol 1,4,5-trisphosphate-dependent Ca2+release and MLCK-mediated MLC20phosphorylation, and 2) sustained contraction exclusively mediated by S1P2involving activation of RhoA via Gαqand Gα13, resulting in Rho kinase- and PKC-dependent MLC20phosphorylation.

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