Increased Rac1 Activation in the Enhanced Carbachol-Induced Bronchial Smooth Muscle Contraction of Repeatedly Antigen-Challenged Mice

Abstract

Recently, we demonstrated that Rac1 upregulation is involved in augmented bronchial smooth muscle (BSM) contractions of antigen-challenged mice. However, change in G protein-coupled receptor (GPCR)induced Rac1 activation remains unknown in BSMs of repeatedly antigen-challenged (Chal.) mice. We here examined carbachol (CCh)-induced Rac1 activation in BSMs of Chal. mice. Gene expression levels of both Rac1 and Rac-guanine nucleotide exchange factors (GEFs), such as Tiam1 and Trio, were increased in BSMs of Chal. mice. Furthermore, CCh-induced Rac1 activation was inhibited by pretreatment with Rac1-GEF inhibitor NSC23766 and Rac1 inhibitor EHT1864 in BSMs of sensitized-control (S.C.) and Chal. mice. Compared with S.C. mice, CCh-induced Rac1 activation was increased in BSMs of Chal. mice. In conclusion, we reported that increased CCh-induced Rac1 activation via Tiam1 and Trio upregulation, in addition to upregulate Rac1, may be involved in increased CCh-induced BSM contractions in Chal. mice.

β‐Catenin is required for optimal exercise‐ and contraction‐stimulated skeletal muscle glucose uptake

“…2013; Kai et al . 2019 a ). NSC23766 blocked EPS‐induced increases in β‐catenin S675 and PAK T423 phosphorylation but did not alter p38 phosphorylation (Fig.…”

“…2015; Kai et al . 2019 a , b ). Carbachol induced phosphorylation of both PAK T423 and β‐catenin S675 , but not β‐catenin S552 in C2C12 myotubes (Fig.…”

“…2015; Kai et al . 2019 a , b ). This suggests the β‐catenin S675 phosphorylation may be sufficient to regulate glucose transport.…”

“…To determine whether Rac1 signalling is required for increased β-catenin S675 phosphorylation during skeletal muscle contraction, we contracted C2C12 myotubes (via EPS) in the presence or absence if the Rac1 inhibitor NSC23766 (Sylow et al 2013;Kai et al 2019a). NSC23766 blocked EPS-induced increases in β-catenin S675 and PAK T423 phosphorylation but did not alter p38 phosphorylation (Fig.…”

A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia

“…Finally, we tested whether the constitutive activation of RAC1 was sufficient to rescue the phenotypes induced by myosin VI depletion using different orthogonal approaches. First, we found that the addition of cholinergic agonist and RAC1 activator carbachol [41, 42] partially rescued the wound closure defect observed upon myosin VI depletion (Figure S3D). Next, we expressed RAC1 wild-type (WT-RAC1) or its fast cycling RAC1-P29S variant [43] in EGFP-LifeAct-expressing cells after silencing of myosin VI.…”