Abstract
The ligands for most of the olfactory receptors (ORs) in mammals remain unknown, because it is difficult to express OR functionally in heterologous cells. It was recently demonstrated that coexpression with the receptor transporting proteins (RTPs) promotes OR functional expression in HEK293T cells. This finding enables us to repeatedly analyze more ORs function in heterologous cells. A murine olfactory receptor OR S6 was cloned from an isolated olfactory receptor neuron (ORN) that responded to octanedioic acid (cc8) and nonanedioic acid (cc9). In this study, we coexpressed RTP1, RTP2, Gα15-olf (Gα15 whose C-terminal seven amino acids are replaced with that of Gαolf) and an OR (OR-S6 or OR-S83) in HEK293 cells. Ligand specificities of ORs were analyzed by using Ca 2+ imaging. We found that HEK293 cells expressing OR-S6 respond to cc8 and cc9 similarly to the original ORN. Furthermore, OR-S83 ligand specificities in HEK293 cells were similar to that in original ORN. Next, we identified novel antagonists for OR-S6 in ligand candidates structurally related to cc8 or cc9. The relationship of structure and activity suggest that ligand length, functional group and interactions between receptor and medial parts of ligands involve in OR-S6 activation. [J Physiol Sci. 2007;57 Suppl:S79]
