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

被引:86
作者
Monte, JC
Nagle, MA
Eraly, SA
Nigam, SK [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
关键词
organic anion transporters; olfactory mucosa; drug transport; OAT6;
D O I
10.1016/j.bbrc.2004.08.112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:429 / 436
页数:8
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