ArticleExperimental & molecular medicine2013
Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.
Article in Experimental & molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 53 citations in OpenAlex.
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- Ion channel molecular complexes in vascular smooth muscle.Frontiers in physiology · 2022Review
- Ameliorative effect and mechanism of Si-Ni-San on chronic stress-induced diarrhea-irritable bowel syndrome in rats.Frontiers in pharmacology · 2022Article
- Ion channels as convergence points in the pathology of pulmonary arterial hypertension.Biochemical Society transactions · 2021Review
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- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Mechanism of contractile dysfunction induced by serotonin in coronary artery in spontaneously hypertensive rats.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Endothelium-Dependent Vasorelaxant Effect ofNutrients · 2019Article
- Estrogen modulates serotonin effects on vasoconstriction through Src inhibition.Experimental & molecular medicine · 2018Article
- KMicrocirculation (New York, N.Y. : 1994) · 2018Review
- Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent KThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- 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 Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- MicroRNA-203 mimics age-related aortic smooth muscle dysfunction of cytoskeletal pathways.Journal of cellular and molecular medicine · 2017Article
- Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Elevated K+ channel activity opposes vasoconstrictor response to serotonin in cerebral arteries of the Fawn Hooded Hypertensive rat.Physiological genomics · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca(2+)-activated K(+), inward rectifier K(+) and ATP-sensitive K(+) channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca(2+) channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, α-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.
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