INTRODUCTION: receptor cells which express the same OR

INTRODUCTION:

Olfactory receptors are presents in every vertebrate which are
involved in the process of olfaction. It is a crucial process which helps in
the eating. Detecting prey or any danger, recreation, detections and overall
life style of living of an individual. The major component of olfactory
receptors is olfactory neurons which are explained in followings. Olfactory
receptors genes are much higher in dogs
and rodents as compared to other vertebrates.

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Olfactory neurons:

The numbers of olfactory neurons in humans being are about ten
million. In vertebrates the olfactory neurons are located in the epithelium of
the olfactory receptors in the nasal cavity. The cell builds of the ORNs are
dispersed amongst all three of the stratified deposits of the olfactory
epithelium.

Structure:

Miniature hair-like cilia project from the olfactory receptor cell’s
dendrite which ends into the mucus casing the exterior of the olfactory
epithelium. A very special protein of G type covered the cilia of the olfactory
neurons. Each olfactory receptor cell states only one type of olfactory
receptor (OR), but many separate olfactory receptor cells express ORs which
bind the same set of odors. The axons of olfactory receptor cells which express
the same OR converge to form glomeruli in the olfactory bulb.

Function:

ORs, which are positioned on the membranes of the cilia, have been
categorized as a complex type of ligand-gated metabotropic channels.
Approximately 1000 different kind of genes code for olfactory receptor which
make them larger gene family. The odor of an odorant first dissolves in the
mucus lining of the olfactory epithelium and then binds to an OR. The affinity
of olfactory receptor is vast and it can bind variety of different kind of odor
molecules.it is the main cause of the alterations in activation patterns
resulting in unique odorant profiles. The activated OR as a result activates
the intracellular G-protein, GOLF (GNAL), adenylate cyclase and production of
cyclic AMP (cAMP) opens ion channels in the cell membrane, resulting in an
influx of sodium and calcium ions into the cell, and an efflux of chloride
ions. Neuron becomes depolarize as a result of influx of positive ions and
efflux of negative ions, causing an action potential.

Desensitization of olfactory neuron:

Negative feedback response of olfactory neurons is very fast on
depolarization. At the time of neuron depolarizing, the CNG ion channel is open
permitting sodium and calcium to flash into the cell. The calcium influx
activates a flow of actions within the cell. Calcium first binds to calmodulin
to form CaM. Cam will stop the sodium and calcium influx when cam binds to the
CNG channel and close it. CaMKII, which will phosphorylate ACIII and decrease
cAMP production, is activated upon the presence of cam. CaMKII will also
activate phosphodiesterase, which will then hydrolyze cAMP. The overall result
of this negative feedback is that it stops the neuron from further activation
when a new molecule of new odor came into the system

Number of distinguishable odors:

According to the scientific research humans can detect about more than
one trillion vast types of odors. There are disputes on these findings as
scientists believe that there are flaws in understanding the olfaction process.
Moreover more research is needed to know the exact number of the odors which
humans can detect.

 

Olfactory Cilia and Disease:

Now Days it is assessed that 3–6 million people suffer from overall or
clinical

Anosmia in the United States alone. It can also be a miscalculate of
the factual number of circumstances, as people are shy and mostly not reported
the lost or transformed sense of smell to their medical doctor. A defect in
olfactory functions can decrease the quality of life and most probably makes
people mood swings. Although the foremost causes of smell disorders in patients
arise following head trauma, upper respiratory tract infections, and chronic
rhino sinusitis, olfactory dysfunction owing to genetic mutations or
neurodegenerative disorders affecting cilia are becoming gradually more
recognized and better studied.

Head trauma:

The trauma of head of all ages is the major cause of the loss of the
sense of smell in patients.

Presently, the largest prevalence of head trauma occurs during a car
accident

52%), with nearly 25% of these cases have malfunctioned olfactory
functions.

The rigorousness ofthe olfactory loss is directly connected with the
severity of the head trauma and period of any posttraumatic amnesia.

The three main causes for the loss of the functions are explained most
probably because of :

(1) Skull or facial fractures causing the interruption of the Sino
nasal tract;

(2) Cutting or tearing of the olfactory nerve bundles

(3) Hemorrhage of the brain region which includes the surrounding of
olfactory bulb or within the bulb.

 

 

 

Chronic rhinosinusitus:

The inflammation of the nasal cavity or mucosa is called as chronic
sinusitis which occurs for at least 12 weeks and is linked with both allergic
and nonallergic rhinitis. The nasal polyps can also be a cause. Representative
symptoms of chronic rhino sinusitiscompriseof nasal obstruction and mucosal
discharge which cause defects in olfactory functions. Theseanosmia’s affect
nearly 10 million people world- wide and account for approximately 25% of all
smell loss cases.

Chronic rhinosinusitus can be occurring due to:

(1) Injury of the olfactory mucosa

(2) Inflammation and loss of 
the OSNs in the epithelium of olfactory.

Mechanism:

Olfactory receptors show affinity for a range of
odor molecules and different olfactory receptors may bind to a single odorant
molecule that depends on physio-chemical properties of molecules like their
molecular volumes. Oncethe odor receptor has bound to odorant, structural changes
occur in receptor molecule and it binds and activates the olfactory-type G
protein on the inside of the olfactory receptor neuron. The G protein (Golfor
Gs) activates the lyase-adenylate cyclase which turnsATP to cyclic
AMP (cAMP). The cAMP opens cyclic nucleotide gated ion channels that allow the
calcium and sodium ions to enter into the cell, depolarizing the olfactory
receptor neuron and initiating an action potential that carries information to
brain.

Primary sequences of varieties of olfactory receptors
are known from the genomes of various organisms.These are seven helix
transmembrane proteins. The exact structures of these proteins are still
unknown. Their sequences exhibit typical class A GPCR motifs that are useful
for building their structures with molecular modeling.

In an advanced explanation, it has been explained
that olfactory receptors could really sense various vibrational energy-levels
of a molecule rather than structural motifs by quantum coherence mechanisms. In
evidence of this explanation it has shown that flies can differentiate between
two different odor molecules that only vary in hydrogen isotope. Beside
differentiating between deuterated and non deuterated forms of an odorant
molecule they can also generalise the properties of deuteratedness.

It is claimed that human olfactory receptors can
differentiate between deuterated and nondeuterated isotopomers of
cyclopentadecanone bysensing vibrational energy level. On the other hand this
claim was challenged by another report that human muskrecognizing receptor
(OR5AN1) thatstrongly responds to cyclopentadecanone and muscone fails to
differentiate isotopomers of these compounds in vitro. It was then concluded
that the proposed vibration theory does not apply to the human musk receptor
OR5AN1and other olfactory receptorsThis later study was also then criticized
that it used cells in a dish rather examining within organisms i.e. applied in
vitro method of examination.

Evolution:

The olfactory receptors in vertebrates have shown
to evolve by genomic mutation events such as gene duplication and gene
conversion. Evidence in favor of gene duplication is provided by the fact that
many olfactory receptor genes belong to the same phylogenetic origin that are
located in the same gene cluster.

Primates have a relatively small number of
functional OR genes as compared to other mammals. The recent hypothesis assumed
that functional OR genes can be correlated to the olfactory ability of a given
organism. In this sense decrease in the number of functional OR genes can cause
a reduction in the sense of smell.Species with higher pseudogene fraction would
also have a decreased olfactory ability. This assumption was flawed as dogs
that are reputed to have good sense of smell do not have the largest number of
functional OR genes. In addition pseudogenes may be functional. 67% of human OR
pseudogenes are expressed in the main olfactory epithelium where they have
regulatory roles in gene expression.

Applications:

·        
Olfactory
receptor neurons have enormous applications in environmental aspects and in in
food quality checking.

·        
Smells are sensed by olfactory sensory neurons in the olfactory epithelium in
vertebrates. The olfactory epithelium is
composed of six different types of cells differing in morphology and in
biochemical properties.

·        
On the other hand in insects
smells are sensed by olfactory sensory neurons in the chemosensory sensilla that are present in insect
antenna, palps and tarsa and on other body parts of insects. Odorants enter into
the cuticle pores of chemosensory sensilla and get attached with insect odorant
binding proteins (OBPs) before activating the sensory neurons that are
responsible for detecting sense of smell.

·        
Olfactory receptors are able to detect air-borne
odour molecules that enter the nasal cavity and bind to olfactory receptors.
The activation of olfactory receptors results in olfactory receptor neurons
sending an impulse to the brain’s olfactory system.

·        
Olfactory receptors are key components in signal
transduction. The sequence and structural analysis of olfactory receptors
provides deep insights to understand their function. In this work, we have
systematically analyzed the relationship between various physical, chemical,
energetic and conformational properties of amino acid residues, and the change
of half maximal effective concentration (EC50) due to amino acid substitutions.
We observed that the odorant molecule (lignad) as well as amino acid properties
are important for EC50. The inclusion of neighboring residues information of
the mutants enhanced the correlation. Further, amino acid properties have been
combined systematically and we obtained a correlation of 0.90-0.98 with
functional data for different (goldfish, mouse and human) olfactory receptors.

Disorders:

The following are disorders of olfaction or olfactory receptors:

ü  Anosmia “inability to smell”

 

o   Anosmia may be temporary, but some forms such
as from an accident, can be permanent.

o   Anosmia is due to a number of factors,
including an inflammation of the nasal mucosa, blockage of nasal passages or a
destruction of one temporal lobe.

 

ü  Dyosmia “things smell different from
memory or expectation”

o   Dyosmia is a disorder described as any
qualitative alteration or distortion of the perception of smell.

o   The cause of dysosmia has not been determined but there have
been clinical associations with the neurological disorder:

§  Upper respiratory tract infection (URTIs)

§  Nasal and paranasal sinus disease

§  Toxic chemical exposure

§  Neurological abnormalities

§  Head trauma

§  Nasal surgery Tumors on the frontal lobe or olfactory bulb

§  Epilepsy

 

ü  Hyposmia “decreased ability to smell”

o   A related condition is anosmia, in which no odors can be
detected.

o   Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. It is estimated that up to 4
million people in the United
States have hyposmia or the related anosmia.

o   Hyposmia might be a very early sign of Parkinson’s disease. Hyposmia is also an early and almost universal finding
in Alzheimer’s disease and dementia
with Lewy bodies. Lifelong hyposmia could be caused
by Kallmann syndrome.

ü  Parosmia ” things smell worse than they
should”

 

o  
One method used to
establish parosmia is the University of Pennsylvania Smell
Identification Test, or UPSIT. “Sniffin’
Sticks” are another method that can be used to properly diagnose parosmia.
These different techniques can also help deduce whether a specific case of
parosmia can be attributed to just one stimulating odor or if there is a group
of stimulating odors that will generate the displaced smell.

o  
Fortunately for
patients afflicted with parosmia, symptoms usually decrease with time.

 

 

ü  Phantosmia
“hallucinated smell” often unpleasant in nature.

 

o  
It can occur in
one nostril or both.

o  
Olfactory
hallucinations can be caused by common medical conditions such as nasal
infections, nasal polyps, or dental problems.

o  
It can result from
neurological conditions such as migraines, head injuries, strokes, Parkinson’s disease, seizures, or brain tumors.

o  
It can also be a
symptom of certain mental disorders such as depression, bipolar disorder,
intoxication or withdrawal from
drugs and alcohol, or psychotic disorders. Environmental
exposures are sometimes the cause as well, such as smoking, exposure to certain
types of chemicals (e.g., insecticides or solvents), or radiation treatment for head or neck cancer.

Conclusion:

Olfactory receptors belong to the super family of G-protein-coupled
receptors (GPCRs), which are characterized by seven transmembrane helical
regions. Olfactory receptors are responsible for checking sense of smell.
Different disorders are also associated with olfactory receptor neurons. Gene
mutations and gene duplications are involved in evolution of olfactory
receptors.