Effects of Y-27632, a Rho/Rho Kinase Inhibitor, on Leukotriene D4- and Histamine-Induced Airflow Obstruction and Airway Microvascular Leakage in Guinea Pigs in vivo

Pharmacology ◽  
2002 ◽  
Vol 64 (4) ◽  
pp. 189-195 ◽  
Author(s):  
Kenichi Tokuyama ◽  
Hideko Nishimura ◽  
Kunihiko Iizuka ◽  
Masahiko Kato ◽  
Hirokazu Arakawa ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Kinase Inhibitor ◽  
Airflow Obstruction ◽  
Rho Kinase ◽  
Microvascular Leakage ◽  
Rho Kinase Inhibitor

scholarly journals Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo

2010 ◽  
Vol 9 (11) ◽  
pp. 875-884 ◽  
Author(s):  
Lin Deng ◽  
Gang Li ◽  
Ronghui Li ◽  
Qinglin Liu ◽  
Qiaowei He ◽  
...  
Keyword(s):  
Cell Line ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell ◽  
Rho Kinase Inhibitor

Fasudil, a Rho-kinase inhibitor, attenuates lipopolysaccharide-induced vascular hyperpermeability and colonic muscle relaxation in guinea pigs

2012 ◽  
Vol 178 (1) ◽  
pp. 352-357 ◽  
Author(s):  
Kensuke Suzuki ◽  
Kayo Nemoto ◽  
Norifumi Ninomiya ◽  
Masamune Kuno ◽  
Minoru Kubota ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Kinase Inhibitor ◽  
Muscle Relaxation ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor

Rho-Kinase Inhibitor Retards Migration and in Vivo Dissemination of Human Prostate Cancer Cells

2000 ◽  
Vol 269 (3) ◽  
pp. 652-659 ◽  
Author(s):  
Avril V. Somlyo ◽  
Dawn Bradshaw ◽  
Susan Ramos ◽  
Cheryl Murphy ◽  
Charles E. Myers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Rho Kinase Inhibitor

Evaluation of Y-27632, a Rho-kinase inhibitor, as a bronchodilator in guinea pigs

2000 ◽  
Vol 406 (2) ◽  
pp. 273-279 ◽  
Author(s):  
Kunihiko Iizuka ◽  
Yasuo Shimizu ◽  
Hideo Tsukagoshi ◽  
Akihiro Yoshii ◽  
Takashi Harada ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
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.

scholarly journals Rho Kinase Inhibitor Fasudil Suppresses the Vasculogenic Mimicry of B16 Mouse Melanoma Cells Both In Vitro and In Vivo

2015 ◽  
Vol 14 (7) ◽  
pp. 1582-1590 ◽  
Author(s):  
Yun Xia ◽  
Xian-Yi Cai ◽  
Ji-Quan Fan ◽  
Li-Ling Zhang ◽  
Jing-Hua Ren ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Vasculogenic Mimicry ◽  
Rho Kinase ◽  
Melanoma Cells ◽  
Mouse Melanoma ◽  
Rho Kinase Inhibitor ◽  
B16 Mouse Melanoma

Abstract 4461: Rho-kinase Pathway Plays an Important Role in the Pathogenesis of Coronary Hyperconstricting Responses Induced by Drug-Eluting Stent

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takashi Shiroto ◽  
Satoshi Yasuda ◽  
Ryuji Tsuburaya ◽  
Yoshitaka Ito ◽  
Hatsue Ishibashi-Ueda ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Bare Metal Stent ◽  
Drug Eluting Stent ◽  
Rho Kinase Inhibitor ◽  
Drug Eluting ◽  
Kinase Expression ◽  
Kinase Pathway

It has recently been reported that coronary vasoconstricting responses are enhanced at the edge of coronary segment implanted with drug-eluting stent (DES) as compared with bare-metal stent (BMS) in humans. We have previously demonstrated in animal models and humans that activation of Rho-kinase plays a key role in the molecular mechanism of coronary vasospasm. In this study, we thus examined whether Rho-kinase pathway also is involved in the DES-induced coronary hyperconstriction in vitro and in vivo. In cultured human coronary vascular smooth muscle cells, paclitaxel (10 –1000 nM, comparable tissue concentrations in humans, 24 hours) concentration-dependently up-regulated Rho-kinase expression (n=9) and increased Rho-kinase activity (10 nM, n=6). In a porcine model in vivo, DES (Taxus ™ ) and BMS (Express ™ ) were randomly implanted in the left anterior descending and circumflex coronary arteries (n=5). Four weeks after the implantation, coronary vasoconstricting responses to serotonin (5-HT, 50 and 100 μg/kg, IC) were significantly enhanced at the DES site compared with the BMS site (DES −52±4 vs. BMS −31±5%, P<0.01), and the enhanced responses were prevented by hydroxyfasudil (HF, 90 and 300 μg/kg, IC), a selective Rho-kinase inhibitor ( Figure A ). The same in vivo findings also were noted in another comparison between DES (Cypher ™ ) and BMS (Velocity ™ ) (DES −62±3% vs. BMS −41±3%, n=6, P<0.01) ( Figure B ). Histological analysis showed microthrombus formation only at the DES site. These results suggest that Rho-kinase pathway also plays an important pathogenetic role in the DES-induced coronary hyperconstricting responses.

The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction, airway hyperresponsiveness, and inflammation

2008 ◽  
Vol 295 (1) ◽  
pp. L214-L219 ◽  
Author(s):  
Dedmer Schaafsma ◽  
I. Sophie T. Bos ◽  
Annet B. Zuidhof ◽  
Johan Zaagsma ◽  
Herman Meurs
Keyword(s):  
Airway Inflammation ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Rho Kinase Inhibitor ◽  
Asthmatic Reaction ◽  
Guinea Pig Model

Recently, we have shown that allergen-induced airway hyperresponsiveness (AHR) after the early (EAR) and late (LAR) asthmatic reaction in guinea pigs could be reversed acutely by inhalation of the Rho kinase inhibitor Y-27632. The present study addresses the effects of pretreatment with inhaled Y-27632 on the severity of the allergen-induced EAR and LAR, the development of AHR after these reactions, and airway inflammation. Using permanently instrumented and unrestrained ovalbumin (OA)-sensitized guinea pigs, single OA challenge-induced EAR and LAR, expressed as area under the lung function (pleural pressure, Ppl) time-response curve, were measured, and histamine PC100 (provocation concentration causing a 100% increase of Ppl) values were assessed 24 h before, and at 6 and 24 h after, the OA challenge (after the EAR and LAR, respectively). Thirty minutes before and 8 h after OA challenge, saline or Y-27632 (5 mM) was nebulized. After the last PC100 value, bronchoalveolar lavage (BAL) was performed, and the inflammatory cell profile was determined. It was demonstrated that inhalation of Y-27632 before allergen challenge markedly reduced the immediate allergen-induced peak rise in Ppl, without significantly reducing the overall EAR and LAR. Also, pretreatment with Y-27632 considerably protected against the development of AHR after the EAR and fully prevented AHR after the LAR. These effects could not be explained by a direct effect of Y-27632 on the histamine responsiveness, because of the short duration of the acute bronchoprotection of Y-27632 (<90 min). In addition, Y-27632 reduced the number of total inflammatory cells, eosinophils, macrophages, and neutrophils recovered from the BAL. Altogether, inhaled Y-27632 protects against acute allergen-induced bronchoconstriction, development of AHR after the EAR and LAR, and airway inflammation in an established guinea pig model of allergic asthma.

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