Olfactory region, location

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. 

One of the lesser functions of the nose in man is that of olfaction. The olfactory region of the nose, a small patch of tissue containing the smell receptors, is located towards the roof of the nasal cavity and is lined with non-ciliated neuro-epithelium. Approximately 20% of the air flowing through the nasal cavity is directed upwards to the olfactory region. Here, bipolar neurones react to inspired air and initiate impulses in the olfactory nerves. 

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... 

By contrast, the accessory olfactory system is thought to be involved in the detection of odors that influence a variety of reproductive and aggressive behaviors (Keverne 1999). Sensory neurons are located in the vomeronasal organ (VNO) and detect pheromones which gain access to the VNO by a pumping mechanism (Meredith and O Connell, 1979). VNO neurons send projections to the accessory olfactory bulb (AOB). Mitral cells of the AOB project in turn to the medial nucleus of the amygdala olfactory information is then dispatched to several hypothalamic regions such as the bed nucleus of the stria terminalis, the medial preoptic area and the ventromedial hypothalamus (Scalia and Winans 1975). 

Several classes of drugs, notably the antipsychotics, discussed in Chapter 34, interfere with dopaminergic transmission. In general, dopamine appears to be an inhibitory neurotransmitter. Five dopamine receptors have been identified the most important and best studied are the Dj. and D2.receptor groups. The Dj receptor, which increases cyclic adenosine monophosphate (cAMP) by activation of adenylyl cyclase, is located primarily in the region of the putamen, nucleus accum-bens, and in the olfactory tubercle. The D2 receptor decreases cAMP, blocks certain calcium channels, and opens certain potassium channels. 

Five subtypes of dopamine receptors have been described they are the Dj-like and Dj-like receptor groups. All have seven transmembrane domains and are G protein-coupled. The Dj-receptor increases cyclic adenosine monophosphate (cAMP) formation by stimulation of dopamine-sensitive adenylyl cyclase it is located mainly in the putamen, nucleus accumbens, and olfactory tubercle. The other member of this family is the D5-receptor, which also increases cAMP but has a 10-fold greater affinity for dopamine and is found primarily in limbic regions. The therapeutic potency of antipsychotic drugs does not correlate with their affinity for binding to the Dj-receptor. 

When the antennae are completely ablated, the male cockroach still responds to the sex pheromone (Roth and Willis, 1952). This suggests that some pheromone-responsive cells are also located elsewhere, such as on the mouthparts. Olfactory receptor cells on the palps of P. americana project to the lobus glomeratus within the posterior region of the ventral deutocerebrum (Boeckh and Ernst, 1987). However, it is not known whether pheromone-responsive cells on the palps project to the more anterior macroglomerulus. 

Mu receptors are almost always located proximally, on the presynaptic side of the synapse. The periaqueductal gray is the region containing the most mu receptors, but they are also found in the superficial dorsal hom of the spinal cord, the external plexiform layer of the olfactory bulb, the nucleus accumbens (an area deeply implicated in the process of addiction), in some parts of the cerebral cortex, and in some of the nuclei of the amygdala. Mu receptors avidly bind enkephalins and beta-endorphin, but they have a low affinity for dynorphins (primarily a kappa receptor agonist).6... 

Figure 14.8 (A) The physical locations of OR, OBP and SNMP (SN) genes are shown on linear representations of the Drosophila chromosomes. All genes are named by map location refer to tables in this chapter for OBPs and SNMPs, and in Voshall, Chapter 19, in this volume, for ORs. Letters following a map number account for multiple genes in that map region. Numbers in parentheses are approximate nucleotide number in megabases (MB) from the top (obtained from the NCBI Map View resource). (B) This illustration suggests that the phenotypes of functionally distinct olfactory sensilla (S.a.-S.e.) are determined by the combinatorial expression of specific members of the indicated olfactory gene families.

What happens at the instant when an odor-active molecule comes in touch with our nasal cavity 205 The first interaction of odorant molecules takes place in the olfactory receptor neurons, which are embedded in the pseudostratified columnar epithelium (or simply, olfactory epithelium), which is located in the posterior nasal cavity in the case of mammals. Olfactory sensory neurons express receptor proteins on the surface membrane of the cilia, which gain access to the extracellular region covered with mucus. The airborne odorants are dissolved into the mucus, bind with the receptors, and then the receptor protein triggers a signal transduction cascade. This results in the opening of the cation channel that would depolarize the sensory neuron and eventually elicit a train of action potentials in the axon. The olfactory axon leads to the olfactory bulb through basal lamina and lamina propria. 

The human nasal cavity, bearing a total surface area of about ISOcm and a total volume of about 15mL, is divided by a midline septum into two non-connected parts. As a cross-sectional view is schematically shown in Fig. lA, the nasal cavity consists of several major differentiated regions. " The nasal vestibule is situated just inside of the nostrils, with an area of about 0.6 cm. The epithelial cells in this region are stratified, squamous, and keratinized. The atrium located at the back of the vestibule is the narrowest region, and has stratified squamous cells anteriorly and pseudostrati-fied cells with microvilli posteriorly. The olfactory... 

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