Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus laevis oocytes

Here, we provide the first evidence for functional expression of a human ol factory receptor protein (OR17-40) and show that recombinant olfactory rece ptors can be functionally expressed in heterologous systems. A mixture of 1 00 different odorants (Henkel 100) elicited a transient increase in intrace llular [Ca2+] in human embryonic kidney 293 (HEK293) cells stably or transi ently transfected with the plasmid pOR17-40. By subdividing the odorant mix ture into progressively smaller groups, we identified a single component th at represented the only effective substance: helional. Only the structurall y closely related molecule heliotroplyacetone also activated the receptor. Other compounds, including piperonal, safrole, and vanillin, were completel y ineffective. Mock-transfected cells and cells transfected with other rece ptors showed no change in intracellular [Ca2+]in response to odor stimulati on. We were also able to functionally express OR17-40 in Xenopus laevis ooc ytes. Coexpression of a "reporter" channel allowed measurement of the respo nse of oocytes injected with the cRNA of the human receptor to the odor mix ture Henkel 100. The effective substances were the same (helional, heliotro pylacetone) as those identified by functionally expressing the receptor in HEK293 cells and were active at the same, lower micromolar concentration. T hese findings open the possibility of now characterizing the sensitivity an d specificity of many, if not all, of the hundreds of different human olfac tory receptors.