更新于：2024-05-01

SLC29A4

solute carrier family 29 member 4

更新于：2024-05-01

基本信息

别名

ENT4、Equilibrative nucleoside transporter 4、FLJ34923

+ [7]

简介

Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs (PubMed:15448143, PubMed:16099839, PubMed:16873718, PubMed:17018840, PubMed:17121826, PubMed:20592246, PubMed:20858707, PubMed:22396231, PubMed:31537831). Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations (PubMed:15448143, PubMed:20592246, PubMed:22396231). Functions as a Na(+)- and Cl(-)-independent bidirectional transporter (PubMed:15448143, PubMed:16099839, PubMed:22396231, PubMed:31537831). Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure (PubMed:16873718, PubMed:17018840, PubMed:20592246, PubMed:22396231, PubMed:31537831). Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system (PubMed:15448143, PubMed:16099839, PubMed:17018840, PubMed:17121826, PubMed:20858707, PubMed:22396231). Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain (By similarity). Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia (PubMed:16873718, PubMed:20592246, PubMed:31537831). May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney (PubMed:17018840). Also transports guanidine (PubMed:16099839).

关联

100 项与 SLC29A4 相关的临床结果

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100 项与 SLC29A4 相关的转化医学

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0 项与 SLC29A4 相关的专利（医药）

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148

项与 SLC29A4 相关的文献（医药）

2024-01-11·International journal of molecular sciences

Cortical and Striatal Astrocytes of Neonatal Rats Display Distinct Molecular and Pharmacological Characteristics of Dopamine Uptake.

Article

作者: Vesna Sočan ; Klemen Dolinar ; Mojca Kržan

Astrocytes are crucial in the regulation of neurotransmitter homeostasis, and while their involvement in the dopamine (DA) tripartite synapse is acknowledged, it necessitates a more comprehensive investigation. In the present study, experiments were conducted on primary astrocyte cultures from the striatum and cortex of neonatal rats. The pharmacological intricacies of DA uptake, including dependence on time, temperature, and concentration, were investigated using radiolabelled [³H]-DA. The mRNA expression of transporters DAT, NET, PMAT, and OCTs was evaluated by qPCR. Notably, astrocytes from both brain regions exhibited prominent mRNA expression of NET and PMAT, with comparatively lower expression of DAT and OCTs. The inhibition of DA uptake by the DAT inhibitor, GBR12909, and NET inhibitors, desipramine and nortriptyline, impeded DA uptake in striatal astrocytes more than in cortical astrocytes. The mRNA expression of NET and PMAT was significantly upregulated in cortical astrocytes in response to the DA receptor agonist apomorphine, while only the mRNA expression of NET exhibited changes in striatal astrocytes. Haloperidol, a DA receptor antagonist, and L-DOPA, a DA precursor, did not induce significant alterations in transporter mRNA expression. These findings underscore the intricate and region-specific mechanisms governing DA uptake in astrocytes, emphasizing the need for continued exploration to unravel the nuanced dynamics of astrocytic involvement in the DA tripartite synapse.

2023-12-06·The European journal of neuroscience

Transporters involved in adult rat cortical astrocyte dopamine uptake: Kinetics, expression and pharmacological modulation.

Article

作者: Vesna Sočan ; Klemen Dolinar ; Mojca Kržan

Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse; however, their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na⁺ -dependent and Na⁺ -independent transporters. Uptake of radiolabelled dopamine was time-, temperature- and concentration-dependent and was inhibited by decynium-22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. Twenty-four-hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L-DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine-tuning of existing therapeutic strategies.

2023-12-01·The Journal of pharmacology and experimental therapeutics

Is Overexpression of the Plasma Membrane Transporter (SLC29A4) a New Option to Stratify Patients with High-Risk Neuroblastoma for Treatment with ¹³¹I-mIBG?

Article

作者: Raymond Evers

项与 SLC29A4 相关的新闻（医药）

2024-03-12

·生物探索

Gut | 山东大学徐云飞/张宗利等合作发现肥大细胞通过胆管癌-胆汁相互作用模式促进胆管癌进展

引言胆汁成分如外泌体或蛋白质可以帮助诊断或预测胆管癌(CCA)的进展，但胆汁代谢物的作用尚未研究。组胺(HA)参与CCA的进展，但HA诱导的进展机制尚不清楚，HA在CCA中的产生和清除尚不清楚。肥大细胞(MC)是肿瘤微环境中一个被忽视的成员。MC在CCA微环境中的作用研究很少。2024年3月8日，山东大学徐云飞、张宗利及吉林大学吕国悦共同通讯在Gut（IF 25）在线发表题为“Function of mast cell and bile-cholangiocarcinoma interplay in cholangiocarcinoma microenvironment”的研究论文，该研究揭示了胆管癌微环境中肥大细胞与胆管癌功能的相互作用。胆汁酸在CCA中升高，表明预后较差。癌症相关成纤维细胞(CAFs)衍生干细胞因子(SCF)募集MCs，胆汁N,N-二甲基-1,4-苯二胺(DMPD)通过G蛋白偶联受体亚型2 (MRGPRX2)-Gαq信号通路刺激MCs释放HA。胆汁诱导的MCs释放血小板衍生生长因子亚单位B (PDGF-B)和血管生成素1/2 (ANGPT1/2)，促进CCA血管生成和淋巴管生成。组胺受体H1 (HRH1)和HRH2分别在CCA细胞和CAFs中主要表达。HA通过激活HRH1-Gαq信号通路促进CCA细胞增殖，通过激活HRH2-Gαs信号通路促进CAFs分泌肝细胞生长因子。溶质载体家族22成员3 (SLC22A3)通过将胆汁HA导入细胞降解抑制HA诱导的CCA增殖，SLC22A3缺失导致HA积累。因此，胆汁HA通过DMPD刺激从MCs中释放，并通过SLC22A3导入降解。不同的HA受体在CCA中表现出不同的表达谱，并产生不同的致癌作用。MCs通过CCA-胆汁相互作用模式促进CCA进展。胆管癌(CCA)是一种起源于胆管的高度侵袭性癌症。体液检查，如尿液检查，对疾病的诊断是重要的，但由于胆汁不能以无创的方式获得，对胆汁检测的研究很少。许多CCA合并胆道狭窄的患者必须进行胆道引流以减少黄疸，使得胆汁含量谱分析成为鉴别恶性或良性胆道狭窄的一种有希望的方法。之前证明了几种蛋白质，如成纤维细胞生长因子7 (FGF7)和高迁移率组盒1 (HMGB1)，或胆汁外泌体中的miRNA，在CCA胆汁中上调，，胆汁成分可以促进CCA进展。然而，小分子在胆汁和CCA进展中的作用很少被研究。组胺(HA)是一种内源性生物胺，参与许多生理功能，特别是局部免疫反应。它还作为大脑、脊髓和子宫的神经递质发挥作用HA存在于所有组织中，含量不同，从小于1到大于100 μg/g不等。皮肤、结缔组织、肺和胃肠道都富含透明质酸。HA主要由组氨酸脱羧酶(HDC)产生，由组胺N-甲基转移酶(HNMT)或胺氧化酶B (MAO-B)代谢透明质酸的清除是一个重要的生理过程，因为透明质酸的积累会导致过度的过敏、炎症或神经元活动。然而，透明质酸如何从组织液转运到细胞中进行清除还没有得到很好的研究。有三种已知的多特异性转运体负责HA转运，它们是溶质载体家族22成员2 (SLC22A2)， SLC22A3和SLC29A4这些受体是低亲和力，高容量和Na+/Cl−不依赖的，但这些受体的组织特异性尚不清楚。CCA中胆汁HA的生成、功能和清除示意图（Credit: Gut）HA通过与其受体，组胺受体(HRH)1/2/3/4相互作用，具有不同的组织特异性表达，具有多种功能HA受体是G蛋白偶联受体(GPCRs)，刺激HA受体可通过偶联不同的G蛋白激活不同的下游信号通路。大多数研究表明，HA-HRH信号的异位刺激具有促肿瘤作用在CCA中，HRH1和HRH2先前被报道参与CCA的肿瘤发生，而HRH3和HRH4被证明抑制CCA的进展。然而，HA受体在CCA中的这些相反作用是有争议的。肥大细胞(MC)是HA储存和释放的主要位置在胆汁淤存或胆管损伤的情况下，MCs可浸润到胆管组织中，据报道MCs可通过释放HA促进CCA进展。此外，先前的研究表明MC来源的HA可促进CCA细胞增殖和分化，但HA的确切功能和触发的信号通路尚未完全揭示。该研究表明，CCA用CAF衍生的SCF募集MCs，胆汁DMPD激活MCs上的MRGPRX2，诱导除HA外PDGF-B和ANGPT1/2的释放。PDGF-B和ANGPT1/2促进血管生成和淋巴管生成。HA通过刺激HRH1 -Gαq信号通路，促进CCA细胞的增殖。另一方面，HA激活HRH2 -Gαs信号，促进CAFs分泌HGF。SLC22A3是HA转运和清除的关键因素。研究发现胆汁HA是一种预测CCA的生物标志物，也是胆汁驱动的CCA进展和胆汁-CCA相互作用的关键效应因子。这些结果表明，胆汁检测是CCA诊断和个体化治疗的新方法。MCs和HA在CCA中的重要性可能有助于发现CCA治疗的新潜在疗法。原文链接https://doi.org/10.1136/gutjnl-2023-331715责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

细胞疗法临床研究