Characterizing Novel Olfactory Receptors Expressed in the Renal Cortex.

The kidney employs specialized G-protein coupled receptors, including olfactory receptors (ORs), to act as sensors of molecules and metabolites. In this study, we cloned and studied 7 renal ORs, which we previously found to be expressed in murine renal cortex. As most ORs are orphan receptors, our goal was to identify ligands for these ORs in the hope that this will guide future research into their functional roles. We identified novel ligands for 2 ORs: Olfr558 and Olfr90. For Olfr558, we confirmed activation by previously reported ligands, and identified 16 additional carboxylic acids that activated this OR. The strongest activation of Olfr558 was produced by butyric, cyclobutanecarboxylic, isovaleric, 2-, 3-, and 4-methylvaleric, and valeric acids. The primary in vivosource of both butyric and isovaleric acids is gut microbial metabolism. We also identified 14 novel ligands that activated Olfr90, the strongest of which were 2-methyl-4-propyl-1,3-oxathiane, 1-octen-3-ol, 2-octanol, and 3-octanol. Interestingly, 8 out of these 14 ligands are of fungal origin. We also investigated the tissue distribution of these receptors, and found that they are each found in a subset of "non-sensory" tissues. Finally, we examined the putative human orthologs of Olfr558 and Olfr90 and found that the human ortholog of Olfr558 (OR51E1) has a similar ligand profile, indicating that the role of this OR is likely evolutionarily conserved. In sum, we examined 7 novel renal ORs, and identified new ligands for Olfr558 and Olfr90, which imply that both of these receptors serve to detect metabolites produced by microorganisms.