Receptors odorant

The difference m odor between (R) and (S) carvone results from their different behavior toward receptor sites m the nose It is believed that volatile molecules occupy only those odor receptors that have the proper shape to accommodate them Because the receptor sites are themselves chiral one enantiomer may fit one kind of receptor while the other enantiomer fits a different kind An analogy that can be drawn is to hands and gloves Your left hand and your right hand are enantiomers You can place your left hand into a left glove but not into a right one The receptor (the glove) can accommodate one enantiomer of a chiral object (your hand) but not the other... 

Olfactory receptors have been a subject of great interest (9). Much that has been postulated was done by analogy to the sense of sight in which there are a limited number of receptor types and, as a consequence, only three primary colors. Thus attempts have been made to recognize primary odors that can combine to produce all of the odors that can be perceived. Evidence for this includes rough correlations of odors with chemical stmctural types and the existence in some individuals having specific anosmias. Cross-adaptation studies, in which exposure to one odorant temporarily reduces the perception of a chemically related one, also fit into this hypothetical framework. Implicit in this theory is the idea that there is a small number of well-defined odor receptors, so that eventually the shape and charge distribution of a specific receptor can be learned and the kinds of molecular stmctures for a specified odor can be deduced. 

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

Enantiomers have identical chemical properties, except when they react with other chiral compounds. Because many biochemical substances are chiral, one consequence of this difference in reactivity is that enantiomers may have different odors and pharmacological activities. The molecule has to fit into a cavity, or slot, of a certain shape, either in an odor receptor in the nose or in an enzyme. Only one member of the enantiomeric pair may be able to fit. 

By far the most studied family of the G-protein-coupled receptors are the rhodopsin-like receptors. These are also the largest group of receptors in number as they include receptors not only for the monoamines, nucleotides, neuropeptides and peptide hormones, but they also include the odorant receptors which number several hundreds of related receptors. These receptors have short N-termini, a conserved disulphide bridge between the TM2-TM3 and TM4—TM5 extracellular domains, and variable-length C-termini. In some cases the C-terminus is myristolyated which by tying the C-terminus to the cell membrane generates a fourth intracellular loop. 

Berghard A. and Dryer L. (1998). A novel family of ancient vertebrate odorant receptors. Neurobiol J 37, 383-392. 

Mombaerts P. (1999). Odorant receptor genes in humans. Curr Opin Genet Dev 9, 315-320. 

Ressler K.J., Sullivan S.L. and Buck L. (1993). Zonal organisation of odorant receptor gene expression in the olfactory epithelium. Cell 73, 597-609. 

Wang F., Nemes A., Mendelsohn M. and Axel R. (1998). Odorant receptors govern the formation of a precise topographic map. Cell 93, 47-60. 

Odor discrimination could involve a very large number of different odorant receptors, each specific for one or a small set of odorants 818 The information generated by hundreds of different receptor types must be organized to achieve a high level of olfactory discrimination 820 Zonal expression of olfactory receptors 821 Convergence of sensory neurons onto a few glomeruli in the olfactory bulb 821... 

FIGURE 50-1 A schematic diagram of the olfactory epithelium. The initial events in odor perception occur in the olfactory epithelium of the nasal cavity. Odorants interact with specific odorant receptors on the lumenal cilia of olfactory sensory neurons. The signals generated by the initial binding events are transmitted along olfactory neuron axons to the olfactory bulb of the brain. 

FIGURE 50-3 Amino acid sequence conservation across mammalian odorant receptors. ORs pass through the plasma membrane (blue box) seven times, with the AT-terminus located extracellularly and the C-terminus intracellularly. The degree of conservation of each amino acid in this consensus OR is indicated by a colored ball, with dark blue being most highly conserved and red most highly variable. Modified from [5], with permission. 

Buck, L. and Axel, R, A novel multigene family may encode odorant receptors a molecular basis for odor recognition. Cell 65 175-187,1991. 

Vassar, R., Ngai, ]. and Axel, R. Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74 309-318,1993. 

Lewcock, ]. W. and Reed, R. R. A feedback mechanism regulates monoallelic odorant receptor expression. Proc. Natl Acad. Sci USA 101 1069-1074, 2004. 

OR odorant receptor PSEP postsynaptic excitatory potential... 

Olfaction, once thought to be a primitive sense, is now recognized as an elaborate sensory system that deploys a large family of odorant receptors to analyse the chemical environment. Interactions between these receptors and their diverse natural binding molecules (ligands) translate the world of odors into a neural code. Humans have about 350 odorant receptors. Rodents have more than a thousand. 

In vertebrates the neurons for olfaction are located in the nose mucosa and consist of short neurons with a peripheral ending endowed with odorant receptors for a large number of molecules in the environment. Each receptor neuron only contains one odorant receptor and is connected directly with the olfactory lobe of the brain. The vertebrate olfactory system must cope with a staggering developmental problem how to connect millions of olfactory neurons expressing different odorant receptors to appropriate targets in the brain. 

All animals exhibit innate behaviors in response to specific sensory stimuli that are likely to result from the activation of developmentally programmed neural circuits. Even the activation of single classes of olfactory neurons can trigger complex behaviors [10]. The authors observed that Drosophila exhibit robust avoidance to odors released by stressed flies. When stressed, the flies emit an odorant mixture that elicits avoidance in other flies. C02 is the active component of this mixture. Specific blockade of the activation of a particular odorant receptor... 

R.V. Friedrich Odorant receptors make scents. Nature 430, 2004. 

In this model, OBPs participate in the selective transport of pheromone and other semiochemicals to their olfactory receptors. The selectivity of the system is likely to be achieved by layers of filters [ 16], i.e., by the participation of compartmentalized OBPs and olfactory receptors. It seems that OBPs transport only a subset of compounds that reach the pore tubules. Some of these compounds may not bind to the receptors compartmentalized in the particular sensilla. The odorant receptors, on the other hand, are activated by a subset of compounds, as indicated by studies in Drosophila, showing that a single OR is activated by multiple compounds [66]. If some potential receptor ligand reaches the pore tubules but are not transported by OBPs, receptor firing is prevented because the receptors are protected by the sensillar lymph. In other words, even if neither OBPs nor odorant receptors (ORs) are extremely specific, the detectors (olfactory system) can show remarkable selectivity if they function in a two-step filter. 

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