OlfactionDB: A Database of Olfactory Receptors and Their Ligands

Abstract

Odorants are volatile molecules that efficiently carry chemical information, providing one of the main ways for communicating with the environment in all kingdoms of life. In the other hand, mammalian genomes codify for hundreds of olfactory receptors (ORs), e.g. about 400 in human and more than 1000 in mouse, underlying the crucial role of the sense of smell during evolution. Therefore, the olfactory system is capable to discriminate between ~10,000 different odors. The possibility of collecting and compiling information about odorants and their receptors is thus fundamental for a functional characterization of the signaling firing event. OlfactionDB, a manually curated database providing comprehensive information for nearly 400 odorant-receptor interactions at the current state, has been developed for managing information about odorants and their receptors. OlfactionDB is a free publicly database available online from: http://molsim.sci.univr.it/OlfactionDB.

Activation of OR1A1 suppresses PPAR-γ expression by inducing HES-1 in cultured hepatocytes

“…The expression of OR1A1 was the highest among the tested ORs, so we performed additional studies. Immunoblotting analysis confirmed that OR1A1 was expressed in the plasma membrane of HepG2 cells, and a previous study demonstrated that (−)-carvone was a strong ligand for OR1A1 (Saito et al, 2009), with a halfmaximal effective concentration of approximately 0.5 M (Modena et al, 2011). The widely distributed natural aroma terpenoid compound, (−)-carvone, which is especially abundant in plant essential oils such as spearmint (Fichan et al, 1999), exhibits antimicrobial, antioxidant, and anti-inflammatory activities (Aggarwal et al, 2002;Elmastas et al, 2006;Terracciano et al, 2006).…”

Shared Ligands Between Organic Anion Transporters (OAT1 and OAT6) and Odorant Receptors

“…This was done by using an online odorant database, OlfactionDB (Modena et al, 2011). Although limited, this database, which is manually curated from the literature, provides information about these odorant molecules and their interactions with odorant receptors (Modena et al, 2011). Since the aim here was to identify odorants that are known to interact with ORs and which might also interact with OATs, it was expected that this database would be useful for virtual screening with the pharmacophore model.…”

“…The pharmacophore model-which has as a basis OR ligands capable of interacting with OATs in transport assays-was then used in a virtual screen of a structural library of odorant molecules which have been shown to bind ORs with an EC 50 of ;1 mM to ;1 mM. This was done by using an online odorant database, OlfactionDB (Modena et al, 2011). Although limited, this database, which is manually curated from the literature, provides information about these odorant molecules and their interactions with odorant receptors (Modena et al, 2011).…”

“…Furthermore, our findings raise the possibility that the transporters and ORs might function in a parallel fashion via their ability to respond to the same or similar ligands. For example, as described above, propionic acid (a gut microbiome-derived short-chain fatty acid) is a substrate for renal organic anion transporters (OAT1/OAT3, Table 1), and this smallmolecule odorant is also able to interact with ORs (OLFR78 and OR51E) (Modena et al, 2011). Interestingly, deletion of renally expressed Olfr78, which also contains the shared motif, results in altered renin secretion and blood pressure regulation (Pluznick et al, 2013).…”

“…These include estrone sulfate, para-aminohippurate (PAH), prostaglandin E 2 (PG-E2) , ibuprofen, and ochratoxin A Kaler et al, 2006;Schnabolk et al, 2006;Truong et al, 2008;Schnabolk et al, 2010). Among the best ligands of this transporter are odorant molecules (Malnic et al, 2010;Modena et al, 2011), many of which also interact with other members of this transporter family, including OAT1 and OAT3 (Kaler et al, 2006(Kaler et al, , 2007. OAT1 [SLC22A6 or novel kidney transporter (NKT)] and OAT3 (SLC22A8) are close homologs that are highly expressed in kidney proximal tubule cells, as well as cells of the choroid plexus and other tissues, where they are responsible for the rate-limiting step in the movement of solutes crossing the bloodurine and blood-cerebrospinal fluid barriers (Lopez-Nieto et al, 1997;Brady et al, 1999;Sweet et al, 2002;Eraly et al, 2006;Ahn and Bhatnagar, 2008;Emami Riedmaier et al, 2012;Nagle et al, 2013;Cesar-Razquin et al, 2015).…”