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Modulation of the olfactory combinatorial code at the periphery

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In the mammalian nose, odorants are detected by odorant receptors (ORs) in a combinatorial fashion: one odorant can activate multiple odorant receptors, and each odorant receptor can detect more than one odorant. (a) When the combinatorial code was first established, each odorant receptor was tested against a given concentration of a single odorant, and only agonist interactions were analyzed. (b) Recent studies that analyzed the responses of odorant receptors to specific odorants presented as part of odor mixtures found that odorants, in addition to their agonist role, can also serve as modulators (antagonists, inverse agonists, partial agonists, and synergistic ligands) to odorant receptor activity. A “No odorant” condition depicts the activation profile of odorant receptors 1 to 6 in the absence of any odorant. Note: An inverse agonist binds to the same receptor as an agonist but brings about the opposite response to that of an agonist, whereas an antagonist binding to such a receptor will disrupt the interaction and the function of both the agonist and the inverse agonist at the receptor. (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)