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.
Keywords:
Rac-guanine nucleotide exchange factor (GEF); Rac1; asthma; bronchial smooth muscle; carbachol.
MeSH terms
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Aminoquinolines / pharmacology
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Animals
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Antigens
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Asthma / genetics
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Asthma / physiopathology
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Bronchi / drug effects
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Bronchi / physiology*
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Carbachol
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / physiology*
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Male
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Mice, Inbred BALB C
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Muscarinic Agonists
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Muscle Contraction / drug effects
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Muscle Contraction / physiology*
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology*
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Neuropeptides / antagonists & inhibitors
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Neuropeptides / genetics
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Neuropeptides / physiology*
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Ovalbumin
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Pyrimidines / pharmacology
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Pyrones / pharmacology
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Quinolines / pharmacology
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T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics
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T-Lymphoma Invasion and Metastasis-inducing Protein 1 / physiology*
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Up-Regulation
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rac1 GTP-Binding Protein / antagonists & inhibitors
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / physiology*
Substances
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Aminoquinolines
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Antigens
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EHT 1864
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Guanine Nucleotide Exchange Factors
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Muscarinic Agonists
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NSC 23766
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Neuropeptides
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Phosphoproteins
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Pyrimidines
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Pyrones
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Quinolines
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Rac1 protein, mouse
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T-Lymphoma Invasion and Metastasis-inducing Protein 1
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Tiam1 protein, mouse
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Trio protein, mouse
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Carbachol
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Ovalbumin
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Protein Serine-Threonine Kinases
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rac1 GTP-Binding Protein