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在嗅觉黏膜中表达的新型小鼠有机阴离子转运蛋白家族成员OAT6的鉴定。

Identification of a novel murine organic anion transporter family member, OAT6, expressed in olfactory mucosa.

作者信息

Monte Julio C, Nagle Megha A, Eraly Satish A, Nigam Sanjay K

机构信息

Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0693, USA.

出版信息

Biochem Biophys Res Commun. 2004 Oct 15;323(2):429-36. doi: 10.1016/j.bbrc.2004.08.112.

Abstract

The organic anion and cation transporters (OATs and OCTs) are a large family (SLC22) of transmembrane proteins that are able to transport a variety of compounds including drugs, environmental toxins, and endogenous metabolites. OATs are expressed in various tissues, primarily kidney and liver, but also in placenta, small intestine, and choroid plexus, which are all epithelial tissues that transport xenobiotics. The upper airway, particularly the nose, is also a site of frequent exposure to environmental toxins. Many drugs are administered intranasally. This raises the possibility that the olfactory epithelium contains OATs and OCTs. Here, we report the identification of a novel putative transporter, mouse OAT6, expressed predominantly in olfactory mucosa but not in kidney or brain. Sequence comparisons and intron phasing analysis indicated that OAT6 is closely related to OAT1 and OAT3. Unlike many other slc22 genes, OAT6 is unpaired in the genome, although it is in proximity to the OAT1/OAT3 gene pair. Expression of OAT6 was also observed in testis. Embryonic expression was observed at day 7, but not later in embryogenesis. This might be due to the need for a key metabolite transported by OAT6. The data raise the possibility that the olfactory mucosa may have a significant transport apparatus which could be important in the design of new therapeutic approaches for direct nose-to-brain transfer of drugs and olfaction. Supporting this possibility, we have demonstrated that OAT1, OCT1-2, and OCTN1-3 are also expressed in olfactory mucosa. Furthermore, e-blot data suggest very different expression of individual OATs, OCTs and OCTNs in kidney, brain, liver, and eye.

摘要

有机阴离子和阳离子转运体(OATs和OCTs)是一个庞大的跨膜蛋白家族(SLC22),能够转运多种化合物,包括药物、环境毒素和内源性代谢物。OATs在各种组织中表达,主要是肾脏和肝脏,但也在胎盘、小肠和脉络丛中表达,这些都是转运外源性物质的上皮组织。上呼吸道,特别是鼻子,也是经常接触环境毒素的部位。许多药物通过鼻腔给药。这增加了嗅觉上皮中含有OATs和OCTs的可能性。在这里,我们报告鉴定出一种新型的假定转运体——小鼠OAT6,其主要在嗅觉黏膜中表达,而在肾脏或大脑中不表达。序列比较和内含子相位分析表明,OAT6与OAT1和OAT3密切相关。与许多其他SLC22基因不同,OAT6在基因组中是不成对的,尽管它与OAT1/OAT3基因对相邻。在睾丸中也观察到了OAT6的表达。在胚胎发育第7天观察到了胚胎期表达,但在胚胎发育后期未观察到。这可能是由于需要OAT6转运的关键代谢物。这些数据增加了嗅觉黏膜可能具有重要转运机制的可能性,这在设计用于药物直接鼻脑转移和嗅觉的新治疗方法中可能很重要。支持这一可能性的是,我们已经证明OAT1、OCT1 - 2和OCTN1 - 3也在嗅觉黏膜中表达。此外,电子印迹数据表明,各个OATs、OCTs和OCTNs在肾脏、大脑、肝脏和眼睛中的表达非常不同。

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