ArticleThe Journal of physiology2014
The small GTPase Rac1 is required for smooth muscle contraction.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Silencing of Rac1 and Arf6 reduces time-dependent and carbachol-induced contractions, proliferation, survival and growth in human bladder smooth muscle cells.World journal of urology · 2025Article
- RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth.Reproduction (Cambridge, England) · 2022Article
- Established and emerging treatments for diabetes-associated lower urinary tract dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Smooth muscle Rac1 contributes to pulmonary hypertension.British journal of pharmacology · 2022Article
- Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder.Biomedicines · 2022Review
- Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2 Phosphorylation.International journal of molecular sciences · 2022Article
- Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Novel computational analysis of large transcriptome datasets identifies sets of genes distinguishing chronic obstructive pulmonary disease from healthy lung samples.Scientific reports · 2021Article
- Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.British journal of pharmacology · 2020Review
- Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766.Frontiers in pharmacology · 2020Article
- The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices.Scientific reports · 2019Article
- Biomechanical characterization of murine pulmonary arteries.Journal of biomechanics · 2019Article
- Vascular smooth muscle contraction in hypertension.Cardiovascular research · 2018Review
- Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: reversal of such metabolic defects by metformin.Apoptosis : an international journal on programmed cell death · 2017Article
- Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors.Scientific reports · 2017Article
- Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders.Pharmacological reviews · 2016Review
- MYPT1 isoforms expressed in HEK293T cells are differentially phosphorylated after GTPγS treatment.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2016Article
- Inhibition of prostate smooth muscle contraction and prostate stromal cell growth by the inhibitors of Rac, NSC23766 and EHT1864.British journal of pharmacology · 2015Article
- Genetic dissection of the vav2-rac1 signaling axis in vascular smooth muscle cells.Molecular and cellular biology · 2014Article
- Smooth muscle specific Rac1 deficiency induces hypertension by preventing p116RIP3-dependent RhoA inhibition.Journal of the American Heart Association · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of the small GTP-binding protein Rac1 in smooth muscle contraction was examined using small molecule inhibitors (EHT1864, NSC23766) and a novel smooth muscle-specific, conditional, Rac1 knockout mouse strain. EHT1864, which affects nucleotide binding and inhibits Rac1 activity, concentration-dependently inhibited the contractile responses induced by several different modes of activation (high-K+, phenylephrine, carbachol and protein kinase C activation by phorbol-12,13-dibutyrate) in several different visceral (urinary bladder, ileum) and vascular (mesenteric artery, saphenous artery, aorta) smooth muscle tissues. This contractile inhibition was associated with inhibition of the Ca2+ transient. Knockout of Rac1 (with a 50% loss of Rac1 protein) lowered active stress in the urinary bladder and the saphenous artery consistent with a role of Rac1 in facilitating smooth muscle contraction. NSC23766, which blocks interaction between Rac1 and some guanine nucleotide exchange factors, specifically inhibited the α1 receptor responses (phenylephrine) in vascular tissues and potentiated prostaglandin F2α and thromboxane (U46619) receptor responses. The latter potentiating effect occurred at lowered intracellular [Ca2+]. These results show that Rac1 activity is required for active contraction in smooth muscle, probably via enabling an adequate Ca2+ transient. At the same time, specific agonists recruit Rac1 signalling via upstream modulators, resulting in either a potentiation of contraction via Ca2+ mobilization (α1 receptor stimulation) or an attenuated contraction via inhibition of Ca2+ sensitization (prostaglandin and thromboxane receptors).
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