Chunyu Zeng, Ines Armando, Jian Yang, Pedro A Jose
{"title":"多巴胺受体D1R和D3R与GRK4在高血压中的相互作用。","authors":"Chunyu Zeng, Ines Armando, Jian Yang, Pedro A Jose","doi":"10.59249/MKRR9549","DOIUrl":null,"url":null,"abstract":"<p><p>Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D<sub>1</sub>-like receptors (D<sub>1</sub>R and D<sub>5</sub>R) stimulate, while D2-like receptors (D<sub>2</sub>R, D<sub>3</sub>R, and D<sub>4</sub>R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D<sub>1</sub>R and D<sub>3</sub>R and their interaction in the natriuresis associated with volume expansion. The D<sub>1</sub>R- and D<sub>3</sub>R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D<sub>3</sub>R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of <i>Drd1</i> and <i>Drd3</i> in mice causes hypertension, <i>DRD1</i> polymorphisms are not always associated with human essential hypertension and polymorphisms in <i>DRD3</i> are not associated with human essential hypertension. The impaired D<sub>1</sub>R and D<sub>3</sub>R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D<sub>1</sub>R and D<sub>3</sub>R. The <i>GRK4</i> locus is linked to and <i>GRK4</i> variants are associated with high blood pressure in humans. Thus, <i>GRK4</i>, by itself, and by regulating genes related to the control of blood pressure may explain the \"apparent\" polygenic nature of essential hypertension.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/b4/yjbm_96_1_95.PMC10052590.pdf","citationCount":"0","resultStr":"{\"title\":\"Dopamine Receptor D<sub>1</sub>R and D<sub>3</sub>R and GRK4 Interaction in Hypertension.\",\"authors\":\"Chunyu Zeng, Ines Armando, Jian Yang, Pedro A Jose\",\"doi\":\"10.59249/MKRR9549\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D<sub>1</sub>-like receptors (D<sub>1</sub>R and D<sub>5</sub>R) stimulate, while D2-like receptors (D<sub>2</sub>R, D<sub>3</sub>R, and D<sub>4</sub>R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D<sub>1</sub>R and D<sub>3</sub>R and their interaction in the natriuresis associated with volume expansion. The D<sub>1</sub>R- and D<sub>3</sub>R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D<sub>3</sub>R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of <i>Drd1</i> and <i>Drd3</i> in mice causes hypertension, <i>DRD1</i> polymorphisms are not always associated with human essential hypertension and polymorphisms in <i>DRD3</i> are not associated with human essential hypertension. The impaired D<sub>1</sub>R and D<sub>3</sub>R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D<sub>1</sub>R and D<sub>3</sub>R. The <i>GRK4</i> locus is linked to and <i>GRK4</i> variants are associated with high blood pressure in humans. Thus, <i>GRK4</i>, by itself, and by regulating genes related to the control of blood pressure may explain the \\\"apparent\\\" polygenic nature of essential hypertension.</p>\",\"PeriodicalId\":48617,\"journal\":{\"name\":\"Yale Journal of Biology and Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/b4/yjbm_96_1_95.PMC10052590.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Yale Journal of Biology and Medicine\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.59249/MKRR9549\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Yale Journal of Biology and Medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.59249/MKRR9549","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
Dopamine Receptor D1R and D3R and GRK4 Interaction in Hypertension.
Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D1-like receptors (D1R and D5R) stimulate, while D2-like receptors (D2R, D3R, and D4R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D1R and D3R and their interaction in the natriuresis associated with volume expansion. The D1R- and D3R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D3R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of Drd1 and Drd3 in mice causes hypertension, DRD1 polymorphisms are not always associated with human essential hypertension and polymorphisms in DRD3 are not associated with human essential hypertension. The impaired D1R and D3R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D1R and D3R. The GRK4 locus is linked to and GRK4 variants are associated with high blood pressure in humans. Thus, GRK4, by itself, and by regulating genes related to the control of blood pressure may explain the "apparent" polygenic nature of essential hypertension.
期刊介绍:
The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.