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Functional Analysis of the Guanylyl Cyclase Type D Signaling System in the Olfactory Epithelium

The mammalian olfactory system recognizes a wide range of chemical stimuli. The majority of cells in the main olfactory epithelium (MOE) use a cAMP‐mediated signaling system to transduce odor signals. However, a subset of MOE neurons instead expresses components of a cGMP signaling cascade, including the receptor guanylyl cyclase GC‐D and the cyclic nucleotide‐gated channel subunit CNGA3. We used a combination of molecular biological, physiological, and imaging approaches to characterize this neuronal population. Neurons expressing GC‐D show excitatory responses to the natriuretic peptide hormones uroguanylin and guanylin, as well as to stimuli present in urine, that are dependent on both GC‐D and CNGA3. Though all GC‐D‐expressing neurons are highly sensitive to these stimuli, individual cells are differentially tuned to either one or both of the peptides. Together, these findings suggest that neurons expressing GC‐D are part of a specialized olfactory subsystem that is responsive to semiochemicals.