Petrol Note in Riesling - 1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) Selectively Activates Human Odorant Receptor OR8H1.

Grapevine (Vitis vinifera) is one of the most important perennial fruit plants. The variety Riesling stands out by developing a characteristic petrol-like odor note during aging, elicited by the aroma compound 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN). The UV-dependent TDN contents differ largely among Rieslings grown in the northern versus the southern hemisphere. Highest TDN concentrations were found in Australian Rieslings, where TDN is a scoring ingredient. In contrast, in Rieslings from Europe, for example, TDN may be a tending cause of rejection. A human receptor for TDN has been unknown. Here, we report on the identification of OR8H1 as a TDN-selective odorant receptor, out of a library of 766 odorant receptor variants. OR8H1 is selectively tuned to six carbon ring structures, identified by screening a collection of 180 key food odorants, using a HEK-293 cell-based cAMP luminescence assay equipped with the GloSensor technology.

Heterodimerization of Chemoreceptors TAS1R3 and mGlu2 in Human Blood Leukocytes.

The expression of canonical chemosensory receptors of the tongue, such as the heteromeric sweet taste (TAS1R2/TAS1R3) and umami taste (TAS1R1/TAS1R3) receptors, has been demonstrated in many extra-oral cells and tissues. Gene expression studies have revealed transcripts for all TAS1 and metabotropic glutamate (mGlu) receptors in different types of immune cells, where they are involved, for example, in the chemotaxis of human neutrophils and the protection of T cells from activation-induced cell death. Like other class-C G protein-coupling receptors (GPCRs), TAS1Rs and mGlu receptors form heteromers within their families. Since mGlu receptors and TAS1R1/TAS1R3 share the same ligand, monosodium glutamate (MSG), we hypothesized their hitherto unknown heteromerization across receptor families in leukocytes. Here we show, by means of immunocytochemistry and co-IP/Western analysis, that across class-C GPCR families, mGlu2 and TAS1R3 co-localize and heterodimerize in blood leukocytes. Expressing the recombinant receptors in HEK-293 cells, we validated their heterodimerization by bioluminescence resonance energy transfer. We demonstrate MSG-induced, mGlu2/TAS1R3 heteromer-dependent gain-of-function and pertussis toxin-sensitive signaling in luminescence assays. Notably, we show that mGlu2/TAS1R3 is necessary and sufficient for MSG-induced facilitation of N-formyl-methionyl-leucyl-phenylalanine-stimulated IL-8 secretion in neutrophils, using receptor-specific antagonists. In summary, our results demonstrate mGlu2/TAS1R3 heterodimerization in leukocytes, suggesting cellular function-tailored chemoreceptor combinations to modulate cellular immune responses.