title: Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaler
authors.forename: David M
authors.initials: DM
authors.lastname: Truong
authors.forename: Derina E
authors.initials: DE
authors.lastname: Sweeney
authors.forename: Darren W
authors.initials: DW
authors.lastname: Logan
authors.forename: Megha
authors.initials: M
authors.lastname: Nagle
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Satish A
authors.initials: SA
authors.lastname: Eraly
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Nigam
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism; D002208:Caproates / Q000378:metabolism; D002478:Cells, Cultured; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D045782:Hemiterpenes; D006537:Heptanoates / Q000378:metabolism; D017136:Ion Transport; D051379:Mice; D009831:Olfactory Mucosa / Q000737:chemistry / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010421:Pentanoic Acids / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012903:Smell
chemical_list: D000838:Anions; D001565:Benzoates; D002087:Butyrates; D002208:Caproates; D045782:Hemiterpenes; D006537:Heptanoates; C492950:OAT6 protein, mouse; D027361:Organic Anion Transporters; D010421:Pentanoic Acids; D011422:Propionates; D012333:RNA, Messenger; C008216:isovaleric acid; D004970:Estrone; C019475:2-methylbutanoic acid; C017296:estrone sulfate