ArticleThe Journal of physiology2008
c-Src tyrosine kinase, a critical component for 5-HT2A receptor-mediated contraction in rat aorta.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Serotonergic Regulation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.Clinical science (London, England : 1979) · 2023Review
- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
- Smooth muscle CaJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Estrogen modulates serotonin effects on vasoconstriction through Src inhibition.Experimental & molecular medicine · 2018Article
- Src tyrosine kinases contribute to serotonin-mediated contraction by regulating calcium-dependent pathways in rat skeletal muscle arteries.Pflugers Archiv : European journal of physiology · 2017Article
- Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2.British journal of pharmacology · 2016Article
- Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- Multiple activation mechanisms of serotonin-mediated contraction in the carotid arteries obtained from spontaneously hypertensive rats.Pflugers Archiv : European journal of physiology · 2016Article
- Diverse effects of a 445 nm diode laser on isometric contraction of the rat aorta.Biomedical optics express · 2015Article
- Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.Experimental & molecular medicine · 2013Article
- The inhibitory effect of Gβγ and Gβ isoform specificity on ENaC activity.American journal of physiology. Renal physiology · 2013Article
- Regulation of L-type calcium channel sparklet activity by c-Src and PKC-α.American journal of physiology. Cell physiology · 2013Article
- Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and Janus kinase-dependent signaling pathway.Molecular and cellular biochemistry · 2013Article
- 5-Hydroxytryptamine 5HT2C receptors form a protein complex with N-methyl-D-aspartate GluN2A subunits and activate phosphorylation of Src protein to modulate motoneuronal depolarization.The Journal of biological chemistry · 2012Article
- Article
- Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Enhancement of mesenteric artery contraction to 5-HT depends on Rho kinase and Src kinase pathways in the ob/ob mouse model of type 2 diabetes.British journal of pharmacology · 2010Article
- Quantitative determination of spatial protein-protein correlations in fluorescence confocal microscopy.Biophysical journal · 2010Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) receptors (5-HTRs) play critical roles in brain and cardiovascular functions. In the vasculature, 5-HT induces potent vasoconstrictions, which in aorta are mainly mediated by activation of the 5-HT(2A)R subtype. We previously proposed that one signalling mechanism of 5-HT-induced vasoconstriction could be c-Src, a member of the Src tyrosine kinase family. We now provide evidence for a central role of c-Src in 5-HT(2A)R-mediated contraction. Inhibition of Src kinase activity with 10 mum 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) prior to contraction resulted in approximately 90-99% inhibition of contractions induced by 5-HT or by alpha-methyl-5-HT (5-HT(2)R agonist). In contrast, PP2 pretreatment only partly inhibited contractions induced by angiotensin II and the thromboxane A(2) mimetic, U46619, and had no significant action on phenylephrine-induced contractions. 5-Hydroxytryptamine increased Src kinase activity and PP2-sensitive tyrosine-phosphorylated proteins. As expected for c-Src identity, PP2 pretreatment inhibited 5-HT-induced contraction with an IC(50) of approximately 1 mum. Ketanserin (10 nm), a 5-HT(2A) antagonist, but not antagonists of 5-HT(2B)R (100 nm SB204741) or 5-HT(2C)R (20 nm RS102221), prevented 5-HT-induced contractions, mimicking PP2 and implicating 5-HT(2A)R as the major receptor subtype coupled to c-Src. In HEK 293T cells, c-Src and 5-HT(2A)R were reciprocally co-immunoprecipitated and co-localized at the cell periphery. Finally, 5-HT-induced Src activity was unaffected by inhibition of Rho kinase, supporting a role of c-Src upstream of Rho kinase. Together, the results highlight c-Src activation as one of the early and pivotal mechanisms in 5-HT(2A)R contractile signalling in aorta.
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