Modulation of the combinatorial code of odorant receptor response patterns in odorant mixtures
| Autor: | Claire A. de March, Hiroaki Matsunami, Patrick Breheny, William B. Titlow, Timothy S. McClintock, Tomoko Sengoku |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist Male medicine.drug_class Sensory system Olfaction Computational biology Biology Receptors Odorant Olfactory Receptor Neurons Article Cellular and Molecular Neuroscience 03 medical and health sciences Lactones Mice 0302 clinical medicine Pentanols medicine Inverse agonist Animals Molecular Biology Cells Cultured G protein-coupled receptor 030304 developmental biology 0303 health sciences Aldehydes Chemistry musculoskeletal neural and ocular physiology Cell Biology Mice Inbred C57BL Smell 030104 developmental biology Odor Odorant Receptor Odorants Female Heterologous expression 030217 neurology & neurosurgery psychological phenomena and processes |
| Zdroj: | Mol Cell Neurosci |
| ISSN: | 1095-9327 |
| Popis: | The perception of odors relies on combinatorial codes consisting of odorant receptor (OR) response patterns to encode odor identity. Modulation of these patterns by odorant interactions at ORs potentially explains several olfactory phenomena: mixture suppression, unpredictable sensory outcomes, and the perception of odorant mixtures as unique objects. We determined OR response patterns to 4 odorants and 3 binary mixtures in vivo in mice, identifying 30 responsive ORs. These patterns typically had a few strongly responsive ORs and a greater number of weakly responsive ORs. ORs responsive to an odorant were often unrelated sequences distributed across several OR subfamilies. Mixture responses predicted pharmacological interactions between odorants, which were tested in vitro by heterologous expression of ORs in cultured cells, providing independent evidence confirming odorant agonists for 13 ORs and identifying both suppressive and additive effects. This included 11 instances of antagonism of ORs by an odorant, 1 instance of additive responses to a binary mixture, 1 instance of suppression of a strong agonist by a weak agonist, and the discovery of an inverse agonist for an OR. Interactions between odorants at ORs are common even when the odorants are not known to interact perceptually in humans, and in some cases interactions at mouse ORs correlate with the ability of humans to perceive an odorant in a mixture. |
| Databáze: | OpenAIRE |
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