Smell, olfactory receptors

Odor and Odorant. That which is smelled. Odor may refer to the odorant or to the sensation resulting from the stimulation of olfactory receptors in the nasal cavity by gaseous material. 

The epithelium covering the nasal cavity. This epithelium contains numerous cell types including the specialized olfactory sensory neurons which detect the chemical stimuli derived from smells by a specific family of G protein-coupled receptors known as olfactory receptors. 

At the cellular level, the various types of receptor, transporter, enzyme and ion charmel are all chiral in form. Thus although the enantiomers of a drug may have identical physicochemical properties, the way in which they may interact with chiral targets at the level of the cell will give rise to different pharmacod)mamic and pharmacokinetic properties. A few simple examples will illustrate how taste and olfactory receptors can differentiate between enantiomers. Thus R-carvone tastes like spearmint whereas the S-isomer tastes like caraway. Similarly, R-limolene smells like lemon whereas the S-enantiomer tastes of orange. 

In humans the olfactory receptor cells lie in the mucous membrane at the top of the air passages on either side of the nasal septum. They occupy a total area of about 2 cm, which is small compared with most other mammals. Evidence from both anatomy and embryology shows that the development of the olfactory tissue is closely linked to that of the pituitary gland which lies at the base of the brain. Among other functions the pituitary plays a key role in the coordination of sexual activity and reproduction. This ancient association between the sense of smell and the reproductive process is one that has important implications for work of the perfumer. 

Figure 5.9 The human olfactory system. (A) Section through the nose. (B) Section through the cribriform plate. (C) The olfactory pathway to the cerebrum (forebrain). This shows the pathway of olfactory sensation. Nasal stimulation begins at the cilia of the olfactory receptor cells located at the ends of the olfactory nerves. The olfactory nerves then carry the impulse to the cerebrum, resulting in the sense of smell.

When a molecule binds with its receptor site the olfactory cells become stimulated and send an impulse along the olfactory nerve. The olfactory nerve is the first cranial nerve. Cranial nerves that carry impulses into the brain are called sensory, while those that carry impulses away are called motor. Sensory information from the olfactory receptors of the nose is carried as a sensory impulse in the olfactory nerve to an area of the brain called the olfactory bulb. It is the olfactory regions of the brain that interpret this sensory information and distinguish different smells. Structures associated with the sense of smell are located in an area of the fore-brain (at the front) called the rhinencephalon. The rhinencephalon is not fully understood and its function is not restricted to olfaction or smelling. The olfactory tract then connects with another area called the neocortex that allows us to be aware of and to recognise odours or smells... 

Vertebrates possess three primary chemosensory systems gustation ( taste ), trigeminal, and olfaction ( smell ) but only one of these, the olfactory system, mediates responses to pheromones. Chemicals that stimulate the olfactory system are known as odorants and comprise one type of biological cue (any entity that stimulates a sensory system). Bouquets of odorants that can be discriminated as specific entities are termed odors. The olfactory system contains olfactory receptor neurons (ORNs) that comprise cranial nerve I and project directly to the forebrain. ORNs are now known to express only one to a few olfactory receptor proteins ( receptors ), which means that the chemoreceptive range of each neuron can be very narrow. The olfactory system also has several subcomponents including the vomeronasal organ, which is described below. 

Q8. (-)-Carvone (73) occurs in spearmint and its enantiomer (+)-carvone (74) is found in caraway seed. To the human sense of smell, these two enantiomers have different odours. Where is the stereogenic centre in 73 and in 74 What conclusions can be drawn about the human olfactory receptor site ... 

In addition to hormone receptors, taste and olfactory receptors are typical examples of this biospecific recognition process. Presumably there are about 20 to 30 primary smells. After being bound to the appropriate receptor, their molecules cause conformational changes in the receptor molecule leading to a depolarization of a part of the nerve cell membranes and initiating an action potential. 

According to stereochemical theory, the mechanism of smell depends on the binding of an odor molecule to a specific receptor site, which resembles the lock-and-key mechanism of enzyme catalysis. If two substances fit the same receptor, they should have the same odor, even if they differ in chemical composition. There are seven different kinds of olfactory receptors, each of which will accept a molecule that has the appropriate geometry. For putrid molecules such as hydrogen sulfide (H2S), however, polarity is more important than shape in linking up with a receptor. In addition, if different portions of a molecule fit different receptors, the molecule should have a mixed odor. For example, portions of benzaldehyde fit the camphor-like, floral, and peppermint receptors we recognize the resulting aroma as almond. 

Most mammals use about 700-800 different types of olfactory receptor proteins in their noses. Humans, chimpanzees, gorillas, orangutans and rhesus macaques use only about half that number. Interestingly, these species are the only animals to possess colour vision and so it would seem that there has been an evolutionary trade-off between smell and colour vision. The rate of loss of olfactory receptor genes is higher in humans than in the other primates, indicating our increased dependence on vision rather than smell (Gilad et al., 2003). 

Breer H., Sense of smell Signal recognition and transduction in olfactory receptor neurons, in Handbook of Biosensors and Electronic Noses Medicine, Food and Environment, ed. E. Kress-Rogers (Boca Raton, EL CRC Press, 1997, 521-532). 

Copper exposures at 20 pg/L or higher induce degenerating effects on the olfactory receptor cells in fish (Saucier and Astic 1995). Since it is a normal process that receptor cells are regenerating in the olfactory epithelium of fish and other vertebrates as long as basal cells are present, new functional olfactory cells will be continuously produced and the animal can recover its sense of smell (e.g. Zippel 1993). There will, however, be problems if the fish remains in contaminated water and the olfactory epithelium does not acclimate and protect the receptor cells from metal toxicity (e.g. by metal-lothioneins, mucus production). It has been shown that olfactory receptor neurons can be a transport route of metal ions and organic molecules to the olfactory bulbs and the brain in vertebrates, fish included, with severe disturbing effects on the function of the CNS (e.g. Tjalve and Henriksson 1999 Persson et al. 2002). 

Olfactory (Smell) Receptors. One example of an olfactory receptor is the olfactory epithelium of the frog/ A number of receptor cells, gathered in a certain place on the skin, produce a receptor potential upon interaction with airborne chemical substances (odorants). The receptor potentials can be summed up to make up a large receptor potential which would evoke an action potential when it exceeds a threshold value. 

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