Inhibition of Agonist-Induced Ca2+Entry in Endothelial Cells by Myosin Light-Chain Kinase Inhibitor

Watanabe, Hiroshi; Takahashi, Reiko; Zhang, Xuxia; Kakizawa, Hiroyasu; Hayashi, Hideharu; Ohno, Ryuzo

doi:10.1006/bbrc.1996.1250

Cited by 55 publications

(44 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Xenopus oocytes, activation of PKC was found to inhibit CCE, 34 whereas in endothelial cells, we showed that inhibitors of PKC and PKA did not affect agonist-induced Ca 2ϩ entry. 35 In the present study, ML-9 and wortmannin abolished TG-and CPA-induced CCE, whereas inhibitors of PTK and PKC had only partial effects. The observations that bisindolylmaleimide I, a strong PKC inhibitor (K i 0.01 mol/L), PKA (K i 2.0 mol/L), 36 and staurosporine only partially inhibited TG-and CPA-induced CCE make it more likely that the effects seen with ML-9 shown in Figure 2A were due to MLCK inhibition.…”

Section: Discussionsupporting

confidence: 45%

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages

Tran

Watanabe

et al. 2001

ATVB

Self Cite

View full text Add to dashboard Cite

Abstract-Monocytes/macrophages are present in all stages of atherosclerosis. Although many of their activities depend to various extents on changes in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ), mechanisms regulating [Ca 2ϩ ] i in these cells remain unclear. We aimed to explore the role of myosin light chain kinase (MLCK) in Ca 2ϩ signaling in freshly isolated human monocytes/macrophages. Large capacitative Ca 2ϩ entry (CCE) was observed under fura 2 fluoroscopy in human monocytes/macrophages treated with thapsigargin and cyclopiazonic acid. ML-9 and wortmannin, 2 structurally different inhibitors of MLCK, dose-dependently (1 to 100 mol/L) prevented CCE and completely did so at 100 mol/L, whereas inhibitors of tyrosine kinase and protein kinase C had only partial effects. Western blotting showed that thapsigargin significantly caused myosin light chain phosphorylation, which was almost completely blocked by ML-9 (100 mol/L) and wortmannin (100 mol/L). ML-9 also dose-dependently (1 to 100 mol/L) inhibited this phosphorylation, which was well correlated with its inhibition of CCE. Transfection with MLCK antisense completely prevented CCE in response to thapsigargin and cyclopiazonic acid, whereas MLCK sense had no effect.

show abstract

Section: Discussionsupporting

confidence: 45%

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages

Tran

Watanabe

et al. 2001

ATVB

Self Cite

View full text Add to dashboard Cite

show abstract

“…143 Smyth et al studied the effect of ML-9 on SOCE in detail and found that ML-9 was equally effective both in preventing SOCE development as well as in inhibiting SOCE following its activation. 144 The effect of ML-9 was reversible and Icrac currents could be restored after ML-9 was washed out.…”

Section: Ml-9mentioning

confidence: 99%

Molecular pharmacology of store-operated CRAC channels

Jairaman

Prakriya

2013

Channels

View full text Add to dashboard Cite

“…Therefore, in our experimental condition, the possibility that cytochalasin D may have some direct inhibitory effect on InsP 3 producing cascade can not be denied. Watanabe et al (14) and Takahashi et al (15) reported the inhibitory effect of ML-9 on TG-and agonist-induced Ca 2+ influx in porcine aortic endothelial cells. Although the morphological studies were not reported in those articles, they speculated the involvement of the cytoskeleton in Ca 2+ entry induced by Ca 2+ store depletion.…”

Section: +mentioning

confidence: 99%

“…In [Ca 2+ ] i mobilization, it has been reported that a MLCK inhibitor attenuates carbachol-activated nonselective cationic current in guinea pig gastric myocytes (13) and also inhibits SOCs in endothelial cells (14,15). Although they suggested the contribution of F-actin on SOCs activation, morphological change in the cells by the agent had not been proposed.…”

Section: +mentioning

confidence: 99%

Integrity of Actin-Network Is Involved in Uridine 5'-Triphosphate Evoked Store-Operated Ca2+ Entry in Bovine Adrenocortical Fasciculata Cells

et al. 2003

View full text Add to dashboard Cite

Abstract. Store-operated Ca 2+ entry channels (SOCs) play an important role in the regulation of diverse non-excitable cell functions. However, the precise mechanism of SOCs activation is still controversial. Uridine 5'-triphosphate (UTP) was shown to induce Ca 2+ entry in a dihydropyridines-insensitive manner and accelerated steroidogenesis in bovine adrenocortical fasciculata cells (BAFCs) via the Gq / 11 protein-coupled P2Y 2 receptor. Therefore we investigated whether UTP is involved in SOCs activation and the mechanism of UTP-induced SOCs activation. Fura 2-loaded BAFCs were used for the measurement of intracellular concentration of Ca ), and the effect of UTP was also attenuated by a phospholipase C inhibitor (U73122). These results indicate that UTP activates SOCs in BAFCs. The increase in [Ca 2+ ] i by UTP was attenuated by ML-9, a myosin-light chain kinase inhibitor, and calmodulin inhibitors, W-7 and E6 berbamine, in a concentration-dependent manner. These reagents depolymerized actin filaments with rhodamine staining in BAFCs. Cytochalasin D also inhibited UTP-activated SOCs and depolymerized actin filaments. From these results, we proposed that calcium / calmodulin dependent myosin-light chain kinase is involved in the mobilization of actin filaments and the integrity of actin-network plays an important role in UTP-induced SOCs activation in BAFCs.

show abstract

Inhibition of Agonist-Induced Ca2+Entry in Endothelial Cells by Myosin Light-Chain Kinase Inhibitor

Cited by 55 publications

References 0 publications

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages

Molecular pharmacology of store-operated CRAC channels

Integrity of Actin-Network Is Involved in Uridine 5'-Triphosphate Evoked Store-Operated Ca2+ Entry in Bovine Adrenocortical Fasciculata Cells

Contact Info

Product

Resources

About

Inhibition of Agonist-Induced Ca2+Entry in Endothelial Cells by Myosin Light-Chain Kinase Inhibitor

Cited by 55 publications

References 0 publications

Myosin Light Chain Kinase Regulates Capacitative Ca 2+ Entry in Human Monocytes/Macrophages

Myosin Light Chain Kinase Regulates Capacitative Ca 2+ Entry in Human Monocytes/Macrophages

Molecular pharmacology of store-operated CRAC channels

Integrity of Actin-Network Is Involved in Uridine 5'-Triphosphate Evoked Store-Operated Ca2+ Entry in Bovine Adrenocortical Fasciculata Cells

Contact Info

Product

Resources

About

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages

Myosin Light Chain Kinase Regulates Capacitative Ca ²⁺ Entry in Human Monocytes/Macrophages