Olfactory sensory cells

The olfactory region located in the poorly accessible recessed roof of the nasal passages offers the potential for certain compounds to circumvent the blood-brain barrier and enter into the brain [48]. The olfactory sensory cells are in contact with both the nasal cavity and the CNS and this neuronal connection constitutes a direct pathway to the brain. By utilizing this pathway drugs would not only circumvent the blood-brain barrier, but also avoid any hepatic first-pass effect and degradation in the blood compartment, a particularly important issue in the case of peptide drugs. 

Signal transduction cascades in olfactory sensory cells... 

Figure 20.1 Olfactory sensory cells of both insects and vertebrates are primary sensory cells, i.e. they are bipolar neurons extending a sensory dendritic process towards the odorous environment and projecting an unbranched axon directly to specialized target regions in the central nervous system.

Getz W. M. and Akers R. P. (1997) Coding properties of peak and average response rates in American cockroach olfactory sensory cells. Biosystems 40, 55-63. 

When each individual olfactory sensory cell should expresse only one specific receptor it would require extraordinarily strict control of gene expression. For the study of gene expression, R.R. Reed and his laboratory have used mutants in Drosophila melanogaster and C. elegans that have defects in olfactory fiuiction. - These studies led to the characterization of olfactory transcription factors, which control the transcription of olfactory receptors. The transcription factor, Olf-1, identified by R. R. Reed, activates a number of olfactory receptor genes. Olf-l is expressed only in olfactory epithelia. It is one of several related, highly conserved transcriptional activators that control the differentiation of olfactory neurons. 

For many marine fish, smell is the primary sense. The olfactory structures are located in the head of a fish, and they sample water from the outside environment by pulling it in through openings called nasal apertures. Water flows into the nasal capsule, a structure that contains olfactory sensory cells. 

Buckley and coworkers (1985) have investigated the inhalation toxicity of dimethy-lamine in F-344 rats and B6C3F1 mice. Animals exposed to 175 ppm for 6 h/day, 5 days/week for 12 months showed significant lesions in the nasal passages. Rats developed more extensive olfactory lesions than did mice. The study indicated that olfactory sensory cells were highly sensitive to dimethylamine. Even at a concentration of 10 ppm, the current threshold limit value, the rodents developed minor lesions from exposure. 

Olfactory sensory cells have axons going directly into the central nervous system, and materials introduced into their cytoplasm via transmembrane uptake in the airway therefore have direct access to the brain side of the blood-brain barrier, via anterograde transport within the cells. 

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. 

Constanzo R. (1991). Regeneration of olfactory receptor cells. In Regeneration of Vertebrate Sensory Cells (Bock G.R., ed.). Wiley, New York, pp. 233-248. 

Schwarting G. and Crandall J. (1991). Subsets of olfactory and vomeronasal sensory cells and axons revealed by MC.Ab to carbohydrate antigens. Brain Res 547, 239-248. 

The ligands for the other forms of membrane-bound GC are less well characterized. In some cases the functions of these GC forms have not been identified. GC-D is expressed in olfactory sensory neurons but its function has not been determined. GC-E and GC-F are expressed in photoreceptor cells in the retina and play a role in phototransduction. GC-G is widely expressed in peripheral tissues and brain but its ligand binding domain is similar to that for GC-A/GC-B, suggesting that it may be regulated by an ANP/BNP-like ligand [34]. 

Vassar, R. et al. Topographic organization of sensory projections to the olfactory bulb. Cell 79 981-991,1994. 

Although pheromones can be considered as a special form of odorants (scents), their actions, effects and functions have similarities to those of hormones. They bind to a specific receptor which then activates an effector system, which initiates an action potential. They bind to specific sensory cells, the neurones, in the olfactory epithelium, which is located on the roof of the nasal cavities. The epithelium consists of three types of cells, basal, supporting and sensory cells (neurones). The neurones are bipolar, that is they possess a single dendrite, which extends from the cell body to the surface of the olfactory epithelium, and an axon that forms a synapse with a nerve that transfers information to the olfactory centre in the brain. The epithelium is covered with a thick layer of mucus, in which the pheromones dissolve. The mucus contains proteins that bind the pheromone(s) for delivery to the olfactory receptors and then to remove them once they have been detected. 

The cyclase produces cAMP which results in opening of a Na" ion channel in the membrane of the sensory cell. If a sufficient number of Na " ions enter, this depolarises the membrane and initiates an action potential along the axon to the olfactory nerve. Further effects depend upon interaction between the nerves and synapses within the olfactory centre in the brain. This can result in physiological effects in other parts of the body which define the function of the pheromone. The effects of pheromones on the sexual responses of men and women are discussed in Chapter 19 (see Figure 19.17). 

The receptors start a second messenger cascade that is initiated by activation of G-proteins in the cell. These, in turn, interact with membrane-bound adenylyl cyclase, which catalyzes the formation of cyclic adenine monophosphate (cAMP) and opening of cAMP-gated cation channels. Depolarization then brings about an action potential, which travels along the axon of the olfactory sensory neuron. Many of the molecular components of this cascade are olfactoiy specific. 

The VNO is lined with bipolar receptor cells (Fig. 5.11). The receptor cells possess microvilli, in contrast to the cilia on the receptor cells of the main olfactory epithelium. The VNO of male and female mice have sensory cells with receptors that respond to male urine, and others that respond to female... 

Differential sensory sensitivity. The insect s perception of plant odours differs essentially from their discrimination of non-volatile taste substances, as phytophagous insects may already perceive the odour at some distance from the plant. In adult phytophagous insects the antennae bear a large number of olfactory sensilla in order to detect the minute concentrations of the leaf odour components in the air downwind from a plant. The overall sensitivity of the antennal olfactory receptor system can be measured by making use of the electroantennogram technique (17). An electroantennogram (EAG) is the change in potential between the tip of an antenna and its base, in response to stimulation by an odour component. Such an EAG reflects the receptor potentials of the olfactory receptor cell population in the antenna. 

Beck. I. H A Quantitative Theory of the Olfactory Threshold Based upon the Amount of the Sensory Cell Covered by an Adsorbed Film. Proc. New York Academy of Sciences, 116, 448 (1964). 

The specialized olfactory mucosa features olfactory sensory neurons, which span the nose-brain barrier. At the epithelial surface nonmotile cilia extend from swellings, which lead via a dendritic extension to the neuronal cell body, from which an extended axon penetrates the... 

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