Dual signal transduction mediated by a single type of olfactory receptor expressed in a heterologous system

Abstract Controversy exists over the relationship between the cAMP and IP3 pathways in vertebrate olfactory signal transduction, as this process is known to occur by either of the two pathways. Recent studies have shown that a single olfactory neuron responds to both cAMP- and IP3-producing odorants, suggesting the existence of an olfactory receptor protein that can recognize both ligands. In this study we found that the rat olfactory receptor I7, stably expressed in HEK-293 cells, triggers the cAMP pathway upon stimulation by a specific odorant (octanal) at concentrations lower than 10-4 M; however, the receptor triggers both pathways at higher concentrations. This indicates that a single olfactory receptor, stimulated by a single pathway-inducing odorant, can evoke both pathways at high odorant concentrations. Using this heterologous system, both the dose-dependent response and receptor I7 specificity were analyzed. The dose-dependent Ca2+ response curve, which also includes the release of Ca2+ ions from internal stores at high odorant concentrations, was not monotonous, but had a local maximum and minimum with 10-10 and 10-7 M octanal, respectively, and reached a plateau at 10-2 M octanal. The specificity of the I7 receptor was lower when exposed to higher concentrations of odorants.

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