{"title":"由β-阿司匹林介导的β-肾上腺素能受体信号转导及其在心力衰竭中的潜在作用","authors":"Preston C Nibley , Sudha K Shenoy","doi":"10.1016/j.cophys.2023.100723","DOIUrl":null,"url":null,"abstract":"<div><p>The lethality of heart failure, particularly in the context of post-acute sequelae SARS-CoV-2 infection-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease. We summarize the signaling mechanisms of the catecholamine-binding β-adrenergic receptors (β-ARs), with an emphasis on the role of β-arrestins. β-ARs, a subset of G protein-coupled receptors (GPCRs), canonically propagate signals through heterotrimeric G proteins. However, since their discovery in the late 1980s, β-arrestins have been shown to both (i) quench G protein signaling and (ii) initiate their own independent signaling cascades, which is influenced by posttranslational modifications<span>. β-arrestin-biased agonism by the beta-blocker carvedilol and its allosteric modulation can serve a cardioprotective role. The increasingly labyrinthine nature of GPCR signaling suggests that ligand-dependent β-AR signaling, either stimulated by an agonist or blocked by an antagonist, is selectively enhanced or suppressed by allosteric modulations, which are orchestrated by novel drugs or endogenous posttranslational modifications.</span></p></div>","PeriodicalId":52156,"journal":{"name":"Current Opinion in Physiology","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure\",\"authors\":\"Preston C Nibley , Sudha K Shenoy\",\"doi\":\"10.1016/j.cophys.2023.100723\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The lethality of heart failure, particularly in the context of post-acute sequelae SARS-CoV-2 infection-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease. We summarize the signaling mechanisms of the catecholamine-binding β-adrenergic receptors (β-ARs), with an emphasis on the role of β-arrestins. β-ARs, a subset of G protein-coupled receptors (GPCRs), canonically propagate signals through heterotrimeric G proteins. However, since their discovery in the late 1980s, β-arrestins have been shown to both (i) quench G protein signaling and (ii) initiate their own independent signaling cascades, which is influenced by posttranslational modifications<span>. β-arrestin-biased agonism by the beta-blocker carvedilol and its allosteric modulation can serve a cardioprotective role. The increasingly labyrinthine nature of GPCR signaling suggests that ligand-dependent β-AR signaling, either stimulated by an agonist or blocked by an antagonist, is selectively enhanced or suppressed by allosteric modulations, which are orchestrated by novel drugs or endogenous posttranslational modifications.</span></p></div>\",\"PeriodicalId\":52156,\"journal\":{\"name\":\"Current Opinion in Physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Physiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2468867323000949\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Physiology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468867323000949","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure
The lethality of heart failure, particularly in the context of post-acute sequelae SARS-CoV-2 infection-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease. We summarize the signaling mechanisms of the catecholamine-binding β-adrenergic receptors (β-ARs), with an emphasis on the role of β-arrestins. β-ARs, a subset of G protein-coupled receptors (GPCRs), canonically propagate signals through heterotrimeric G proteins. However, since their discovery in the late 1980s, β-arrestins have been shown to both (i) quench G protein signaling and (ii) initiate their own independent signaling cascades, which is influenced by posttranslational modifications. β-arrestin-biased agonism by the beta-blocker carvedilol and its allosteric modulation can serve a cardioprotective role. The increasingly labyrinthine nature of GPCR signaling suggests that ligand-dependent β-AR signaling, either stimulated by an agonist or blocked by an antagonist, is selectively enhanced or suppressed by allosteric modulations, which are orchestrated by novel drugs or endogenous posttranslational modifications.