A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium

Abstract

Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca 2+ imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30 µm). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing.

A G protein/cAMP signal cascade is required for axonal convergence into olfactory glomeruli

“…One hundred percent of octanal-responsive GFP ϩ OSNs displayed the expected ORI7 profile, thus confirming that HA-ORI7 is functional (n ϭ 6). For comparison, similar to our previous study (20), only 13% of the octanal-responsive GFP Ϫ OSNs possessed an ORI7-like profile (n ϭ 15). From the calcium imaging experiments, we conclude that the exogenous HA-ORI7 alters the odorant response properties of OSNs in an expected manner.…”

“…Calcium imaging was performed as reported (20). Dual luciferase assays were performed per the manufacturer's instructions (Promega, Madison, WI).…”

A Large-Scale Analysis of Odor Coding in the Olfactory Epithelium

“…Knowledge of what OSNs recognize and how they are used to encode odor identities is therefore crucial to understanding how sensory inputs are processed in the brain to ultimately yield odor perceptions. Important insights into this question have come from studies of OSN and OR responses to varied odorants (Sato et al, 1994;Duchamp-Viret et al, 1999;Malnic et al, 1999;Araneda et al, 2004;Saito et al, 2009). However, due to the relatively small number of different OSN/OR-odorant combinations tested, a broad understanding of odor coding by the OSN/OR repertoire is still lacking.…”

Competitive and Noncompetitive Odorant Interactions in the Early Neural Coding of Odorant Mixtures

“…With a few exceptions, each ORN expresses only one of their OR genes. Each OR can recognize several odorants, and each odorant can be recognized by more than one OR, each odorant-OR interaction being characterized by a specific affinity (Araneda et al, 2004;Sanz et al, 2005).…”