ArticleBritish journal of pharmacology2008
Novel interactions between the 5-HT transporter, 5-HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts.
Article in British journal of pharmacology, 2008. 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, 42 citations in OpenAlex.
- The serotonin receptor 2b (5-HTiScience · 2026Article
- Review
- Fatty acid-binding protein 5 aggravates pulmonary artery fibrosis in pulmonary hypertension secondary to left heart disease via activating wnt/β-catenin pathway.Journal of advanced research · 2022Article
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Rho kinase inhibitor fasudil reduces l-DOPA-induced dyskinesia in a rat model of Parkinson's disease.British journal of pharmacology · 2020Article
- Cellular Pathways Promoting Pulmonary Vascular Remodeling by Hypoxia.Physiology (Bethesda, Md.) · 2020Review
- The Role and Regulation of Pulmonary Artery Smooth Muscle Cells in Pulmonary Hypertension.International journal of hypertension · 2020Review
- Interactions Between the Serotonergic and Other Neurotransmitter Systems in the Basal Ganglia: Role in Parkinson's Disease and Adverse Effects of L-DOPA.Frontiers in neuroanatomy · 2020Review
- Connexin 43 Plays a Role in Pulmonary Vascular Reactivity in Mice.International journal of molecular sciences · 2018Article
- Serotonin Signaling Through the 5-HTArteriosclerosis, thrombosis, and vascular biology · 2017Article
- Lung Circulation.Comprehensive Physiology · 2016Review
- A Sex-Specific MicroRNA-96/5-Hydroxytryptamine 1B Axis Influences Development of Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2015Article
- Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Vascular remodeling in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2013Review
- In utero exposure to antidepressants and the use of drugs for pulmonary diseases in children.European journal of clinical pharmacology · 2013Article
- Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus.American journal of physiology. Lung cellular and molecular physiology · 2011Article
- Mice lacking the Raf-1 kinase inhibitor protein exhibit exaggerated hypoxia-induced pulmonary hypertension.British journal of pharmacology · 2011Article
- Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies.Circulation · 2010Review
- Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.British journal of pharmacology · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeWhile the 5-HT and Rho-kinase (ROCK) pathways have been implicated in the development of pulmonary arterial hypertension (PAH), the nature of any interactions between them remain unclear. This study investigated a role for ROCK in 5-HT-regulated proliferative responses in lung fibroblasts in vivo and in vitro. EXPERIMENTAL APPROACH: PAH was examined in mice over-expressing human 5-HT transporters (SERT+), from which pulmonary artery fibroblasts (PFs) were isolated to assess ROCK expression. In vitro analysis of 5-HT signalling employed CCL39 hamster lung fibroblasts. KEY
resultsROCK inhibition ablated increased pulmonary remodelling and hypertension observed in SERT+ mice, and ROCK1/2 protein levels were elevated in SERT+ PFs. ROCK inhibition also reduced 5-HT-stimulated proliferation by suppressing MEK-stimulated ERK phosphorylation. While optimal 5-HT-stimulated proliferation required 5-HT(1B) and 5-HT(2A) receptors and SERT, receptor sensitivity to Y27632 was restricted to the 5-HT(1B) receptor. Also, while hypoxia-induced pulmonary vascular remodelling and hypertension were sensitive to Y27632 in WT and SERT+ animals, the proportions sensitive to ROCK inhibition were increased by SERT over-expression. CONCLUSIONS AND IMPLICATIONS: SERT over-expression increased ROCK-dependent pulmonary remodelling in normoxia and hypoxia and SERT over-expression was associated with elevated ROCK1/2 levels. ROCK also potentiated 5-HT(1B) receptor-stimulated ERK activation and proliferation in vitro by facilitating MEK-ERK interaction.
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