Kaler Gregory, Truong David M, Sweeney Derina E, Logan Darren W, Nagle Megha, Wu Wei, Eraly Satish A, Nigam Sanjay K
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):872-6. doi: 10.1016/j.bbrc.2006.10.136. Epub 2006 Nov 2.
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 Oat1 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.
我们已经对有机阴离子转运蛋白6（Oat6，即slc22a20）在嗅觉黏膜中的表达及其与几种气味有机阴离子的相互作用进行了表征。原位杂交显示Oat6在整个嗅觉上皮中呈弥漫性表达，但从主嗅觉上皮（MOE）或犁鼻器（VNO）激光捕获显微切割得到的嗅觉神经元并不表达Oat6 mRNA。这些数据表明，Oat6在嗅觉组织的非神经元细胞中表达，如上皮细胞和/或其他支持细胞。接下来，我们研究了Oat6与几种先前已被确定为小鼠尿液中气味类型成分的小有机阴离子之间的相互作用。我们发现，这些化合物中的每一种，即丙酸、2-甲基丁酸、3-甲基丁酸、苯甲酸、庚酸和2-乙基己酸，都能抑制Oat6介导的标记示踪剂硫酸雌酮的摄取，这与其作为Oat6底物的特性相符。此前，我们注意到Oat1基因敲除小鼠在肾脏对气味类型和气味类型样分子的清除方面存在缺陷。这些分子与Oat6相互作用的发现增加了一种可能性，即通过一种OAT介导机制（Eraly等人，《生物化学杂志》2006年）分泌到尿液中的气味剂，可能通过另一种OAT介导机制穿过嗅觉黏膜进行转运。Oat6可能在嗅觉中发挥直接或间接作用，例如调节黏膜表面气味有机阴离子的可利用性，以便呈现给嗅觉神经元，或者促进其传递到化学感受的远端部位，以及我们所讨论的其他可能性。
