5‐Hydroxytryptamine and Atrial Fibrillation:

Yusuf, Shamil; Al-Saady, N.; Camm, A. John

doi:10.1046/j.1540-8167.2003.02381.x

Cited by 42 publications

(4 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even if this proarrhythmic effect of fluoxetine is usually explained by hERG (Kv11.1, a K ϩ channel; for a review, see Ref. 54) and/or L-type Ca 2ϩ current inhibition (42), fluoxetine treatment might increase cardiac levels of 5-HT that can cause cardiac arrhythmias in humans, as mentioned above (58). Our findings might explain, at least in part, these clinical observations.…”

Section: Discussionmentioning

confidence: 53%

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts

Gergs

Jung

Buchwalow

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Using transgenic (TG) mice that overexpress the human serotonin (5-HT) receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again increase the interest of researchers for cardiac effects of 5-HT.

show abstract

Section: Discussionmentioning

confidence: 53%

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts

Gergs

Jung

Buchwalow

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Serotonin, 5-hydroxytryptamine, is a hormonal trigger for AF [ 45 , 46 ]. By a KEGG analysis, we found that pathways are related to the role of WXKL in AF including the regulation of serotonergic synapses and tryptophan metabolism.…”

Section: Discussionmentioning

confidence: 99%

Molecular Targets and Pathways Contributing to the Effects of Wenxin Keli on Atrial Fibrillation Based on a Network Pharmacology Approach

Zhang

Zhang²,

Zhang³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with high rates of mortality and morbidity. The traditional Chinese medicine Wenxin Keli (WXKL) can effectively improve clinical symptoms and is safe for the treatment of AF. However, the active substances in WXKL and the molecular mechanisms underlying its effects on AF remain unclear. In this study, the bioactive compounds in WXKL, as well as their molecular targets and associated pathways, were evaluated by systems pharmacology. Materials and Methods. Chemical constituents and potential targets of WXKL were obtained via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). The TTD, DrugBank, DisGeNET, and GeneCards databases were used to collect AF-related target genes. Based on common targets related to both AF and WXKL, a protein interaction network was generated using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses were performed. Network diagrams of the active component-target and protein-protein interactions (PPIs) were constructed using Cytoscape. Results. A total of 30 active ingredients in WXKL and 219 putative target genes were screened, including 83 genes identified as therapeutic targets in AF; these overlapping genes were considered candidate targets for subsequent analyses. The effect of treating AF was mainly correlated with the regulation of target proteins, such as IL-6, TNF, AKT1, VEGFA, CXCL8, TP53, CCL2, MMP9, CASP3, and NOS3. GO and KEGG analyses revealed that these targets are associated with the inflammatory response, oxidative stress reaction, immune regulation, cardiac energy metabolism, serotonergic synapse, and other pathways. Conclusions. This study demonstrated the multicomponent, multitarget, and multichannel characteristics of WXKL, providing a basis for further studies of the mechanism underlying the beneficial effects of WXKL in AF.

show abstract

“…5-HT elevates cAMP content and regulates the concentration of Ca 2+ through 5-HT 4 receptors in human atrial cardiomyocytes [6]. 5-HT 4 receptors were detected in human sinoatrial node and atrial cardiomyocytes; activation of these receptors causes a positive inotropic, chronotropic, lusitropic effects, tachicardia and atrial fibrillation [10,11,15].Hence, the serotoninergic system is involved in the functioning of the cardiovascular system and in the pathogenetic mechanisms of its diseases. However, the role of 5-HT in the regulation of cardiac inotropic function during human postnatal ontogenesis in various congenital heart diseases remains poorly studied.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Functional activity of 5-HT4 receptors in children with congenital heart disease

2006

View full text Add to dashboard Cite

The effect of 5-methoxytryptamine (5-HT(4) receptor agonist) on the inotropic function of atrial myocardium was studied in children aged 2 months to 17 years, operated on for congenital heart disease. Functional activity of 5-HT(4) receptors was 8.4 times higher in dysfunction of the atrial septum in comparison with other congenital heart diseases. The positive inotropic effects of 5-HT(4) receptor agonist can promote compensation of myocardial work in children with pathological circulation.

show abstract

5‐Hydroxytryptamine and Atrial Fibrillation:

Cited by 42 publications

References 83 publications

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts

Molecular Targets and Pathways Contributing to the Effects of Wenxin Keli on Atrial Fibrillation Based on a Network Pharmacology Approach

Functional activity of 5-HT4 receptors in children with congenital heart disease

Contact Info

Product

Resources

About