Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions
Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions
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DOI：
10.1016/j.bbrc.2006.10.136
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发表时间：
2006-12-29
影响因子：
3.1
通讯作者：
Nigam, Sanjay K.
中科院分区：
文献类型：
--
作者：
Kaler, Gregory;Truong, David M.;Nigam, Sanjay K.
我们的特点是表达的有机阴离子转运体6，Oat 6（slc 22 a20），在嗅粘膜，以及它与几种气味的有机阴离子的相互作用。原位杂交显示Oat 6在整个嗅上皮的表达，但嗅觉神经元激光捕获显微解剖的主要嗅上皮（莫伊）或犁鼻器（VNO）不表达Oat 6 mRNA。这些数据表明，Oat 6在嗅觉组织的非神经元细胞中表达，例如上皮细胞和/或其他支持细胞。接下来，我们研究了Oat 6与几种小的有机阴离子的相互作用，这些阴离子先前已被鉴定为小鼠尿液中的气味成分。我们发现，这些化合物，丙酸，2-和3-甲基丁酸，苯甲酸，庚酸，和2-乙基己酸，抑制Oat 6介导的摄取标记示踪剂，硫酸雌酮，与它们是Oat 6底物一致。先前，我们注意到Oat]敲除小鼠中气味型和气味型样分子的肾脏消除缺陷。这类分子与Oat 6相互作用的发现提高了气味剂通过一种OAT介导的机制分泌到尿液中的可能性（Eraly et al.，JBC 2006）通过另一种OAT介导的机制通过嗅粘膜转运。燕麦6可能发挥直接或间接的作用，嗅觉，如调制的可用性的气味有机阴离子在粘膜表面的嗅觉神经元或促进交付到一个远端网站的化学感觉，我们讨论的其他可能性。(c)2006年爱思唯尔公司All rights reserved.
We have characterized the expression of organic anion transporter 6, Oat6 (slc22a20), in olfactory mucosa, as well as its interaction with several odorant organic anions. In situ hybridization reveals diffuse Oat6 expression throughout olfactory epithelium, yet olfactory neurons laser-capture microdissected from either the main olfactory epithelium (MOE) or the vomeronasal organ (VNO) did not express Oat6 mRNA. These data suggest that Oat6 is expressed in non-neuronal cells of olfactory tissue, such as epithelial and/or other supporting cells. We next investigated interaction of Oat6 with several small organic anions that have previously been identified as odortype components in mouse urine. We find that each of these compounds, propionate, 2- and 3-methylbutyrate, benzoate, heptanoate, and 2-ethylhexanoate, inhibits Oat6-mediated uptake of a labeled tracer, estrone sulfate, consistent with their being Oat6 substrates. Previously, we noted defects in the renal elimination of odortype and odortype-like molecules in Oat] knockout mice. The finding that such molecules interact with Oat6 raises the possibility that odorants secreted into the urine through one OAT-mediated mechanism (Eraly et al., JBC 2006) are transported through the olfactory mucosa through another OAT-mediated mechanism. Oat6 might play a direct or indirect role in olfaction, such as modulation of the availability of odorant organic anions at the mucosal surface for presentation to olfactory neurons or facilitation of delivery to a distal site of chemosensation, among other possibilities that we discuss. (c) 2006 Elsevier Inc. All rights reserved.