Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho.

IF 4.2 2区 医学 Q1 PHYSIOLOGY
Margaret R MacLean, Barry Fanburg, Nicolas Hill, Howard M Lazarus, Thomas F Pack, Michelle Palacios, Krishna C Penumatsa, Stephen A Wring
{"title":"Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho.","authors":"Margaret R MacLean, Barry Fanburg, Nicolas Hill, Howard M Lazarus, Thomas F Pack, Michelle Palacios, Krishna C Penumatsa, Stephen A Wring","doi":"10.1002/cphy.c220004","DOIUrl":null,"url":null,"abstract":"<p><p>Serotonin is often referred to as a \"happy hormone\" as it maintains good mood, well-being, and happiness. It is involved in communication between nerve cells and plays a role in sleeping and digestion. However, too much serotonin can have pathogenic effects and serotonin synthesis is elevated in pulmonary artery endothelial cells from patients with pulmonary arterial hypertension (PAH). PAH is characterized by elevated pulmonary pressures, right ventricular failure, inflammation, and pulmonary vascular remodeling; serotonin has been shown to be associated with these pathologies. The rate-limiting enzyme in the synthesis of serotonin in the periphery of the body is tryptophan hydroxylase 1 (TPH1). TPH1 expression and serotonin synthesis are elevated in pulmonary artery endothelial cells in patients with PAH. The serotonin synthesized in the pulmonary arterial endothelium can act on the adjacent pulmonary arterial smooth muscle cells (PASMCs), adventitial macrophages, and fibroblasts, in a paracrine fashion. In humans, serotonin enters PASMCs cells via the serotonin transporter (SERT) and it can cooperate with the 5-HT1B receptor on the plasma membrane; this activates both contractile and proliferative signaling pathways. The \"serotonin hypothesis of pulmonary hypertension\" arose when serotonin was associated with PAH induced by diet pills such as fenfluramine, aminorex, and chlorphentermine; these act as indirect serotonergic agonists causing the release of serotonin from platelets and cells through the SERT. Here the role of serotonin in PAH is reviewed. Targeting serotonin synthesis or signaling is a promising novel alternative approach which may lead to novel therapies for PAH. © 2022 American Physiological Society. Compr Physiol 12: 1-16, 2022.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comprehensive Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cphy.c220004","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Serotonin is often referred to as a "happy hormone" as it maintains good mood, well-being, and happiness. It is involved in communication between nerve cells and plays a role in sleeping and digestion. However, too much serotonin can have pathogenic effects and serotonin synthesis is elevated in pulmonary artery endothelial cells from patients with pulmonary arterial hypertension (PAH). PAH is characterized by elevated pulmonary pressures, right ventricular failure, inflammation, and pulmonary vascular remodeling; serotonin has been shown to be associated with these pathologies. The rate-limiting enzyme in the synthesis of serotonin in the periphery of the body is tryptophan hydroxylase 1 (TPH1). TPH1 expression and serotonin synthesis are elevated in pulmonary artery endothelial cells in patients with PAH. The serotonin synthesized in the pulmonary arterial endothelium can act on the adjacent pulmonary arterial smooth muscle cells (PASMCs), adventitial macrophages, and fibroblasts, in a paracrine fashion. In humans, serotonin enters PASMCs cells via the serotonin transporter (SERT) and it can cooperate with the 5-HT1B receptor on the plasma membrane; this activates both contractile and proliferative signaling pathways. The "serotonin hypothesis of pulmonary hypertension" arose when serotonin was associated with PAH induced by diet pills such as fenfluramine, aminorex, and chlorphentermine; these act as indirect serotonergic agonists causing the release of serotonin from platelets and cells through the SERT. Here the role of serotonin in PAH is reviewed. Targeting serotonin synthesis or signaling is a promising novel alternative approach which may lead to novel therapies for PAH. © 2022 American Physiological Society. Compr Physiol 12: 1-16, 2022.

羟色胺与肺动脉高压;性与药物以及 ROCK 与 Rho。
羟色胺通常被称为 "快乐激素",因为它能保持良好的情绪、幸福和快乐。它参与神经细胞之间的交流,并在睡眠和消化中发挥作用。然而,过多的血清素会产生致病作用,肺动脉高压(PAH)患者的肺动脉内皮细胞中的血清素合成会升高。肺动脉高压的特点是肺压升高、右心室衰竭、炎症和肺血管重塑;血清素已被证明与这些病症有关。在人体外周合成血清素的限速酶是色氨酸羟化酶 1(TPH1)。在 PAH 患者的肺动脉内皮细胞中,TPH1 的表达和血清素的合成都会升高。肺动脉内皮细胞合成的血清素可通过旁分泌方式作用于邻近的肺动脉平滑肌细胞(PASMC)、临近的巨噬细胞和成纤维细胞。在人体中,血清素通过血清素转运体(SERT)进入 PASMCs 细胞,并与质膜上的 5-HT1B 受体合作,从而激活收缩和增殖信号通路。5-羟色胺与芬氟拉明、阿米诺雷克斯和氯苯特明等减肥药诱发的 PAH 有关,从而提出了 "5-羟色胺肺动脉高压假说";这些减肥药是间接的 5-羟色胺能激动剂,可通过 SERT 从血小板和细胞中释放 5-羟色胺。在此回顾一下血清素在 PAH 中的作用。以血清素合成或信号传导为靶点是一种很有前景的新型替代方法,可为 PAH 带来新型疗法。© 2022 美国生理学会。Compr Physiol 12: 1-16, 2022.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信