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NEUROTRANSMITTERS

M.Prasad Naidu
MSc Medical Biochemistry, Ph.D,.

Neurotransmitters

Definition:

Neruo transmitters are endogenous chemicals
which transmit signals from a neuron to target cells
across a synapse.



Important Neuro transmitters are

1. GABA
2. Serotonin
3. Acetyl choline
4. Catecholamines
Dopa
Norepinephrine
Epinephrine
5. Glycine
6. Glutamate

Miscellaneous:

Nitric oxide
Taurine
Histamine
Aspartate



Name of the
neurotransmitter
Excitatory Inhibitory
1. GABA ----- Inhibitory
2. Catecholamines Excitatory -----
3. Glycine --- Inhibitory
4. Glutamate Excitatory ----
5. Acetyl choline Excitatory -----
6. Serotonin
GABA
amino butyric acid
Synthesized from A.A L- glutamate by decarboxylation.

Glutamate decarboxylase
Glutamate GABA
PLP

CO
2


Glutamate decarboxylase is present in nerve endings
of the brain as well as in the -cells of the pancreas.




GABA increase the permeability of post synaptic
membranes to chloride ions.

GABA act as neurotransmitter by opening of the
chloride ion channels.


Glutamate

Non essential Aminoacid
Excitatory neurotransmitter,
Neurons contain NMDA(N methyl D Aspartate )
receptors.
NMDA receptors are stimulated by glutamate and
opens calcium channel leading to stimulation of
neuronal NOS (Nitric oxide synthase)and produces
NO.

NO activates guanyl cyclase, there by increasing
cyclic GMP in neighboring neurons and causes
excitation .

Glutamate NMDA receptors

Activates NOS

NO

Guanylcyclase

CyclicGMP

Excitation of Neurons


In conditions like head injury , Huntingtons chorea
etc., cerebral damage causes

Excess glutamate is released in brain.

This increased glutamate causes increased release of
calcium, generation of free radicals and cell death.


Serotonin

Serotonin is excitatory on motor pathways and inhibitory
on sensory pathways
Synthesized from tryptophan



Synthesis of Serotonin

5-Hydroxy tryptophan on decarboxylation produces
serotonin A neurotransmitter



5-Hydroxy tryptophan Serotonin
Decarboxylase

Tryptophan hydroxylase
Decarboxylase
Mono amino
Oxidase
Acetalyse
Methyal
transferase
Serotonin

Serotonin is involved in mood changes
Sleep
Appetite and
Temperature regulation
Increases intestinal motility

Decreased levels is seen in depressive
psychosis.
Glycine

Inhibitory neuro transmitter in the spinal cord.

It blocks impulses traveling down in cord in motor
neurons to stimulate skeletal muscle

It increases chloride ions and produces hyper
polarisation at post synaptic neurons

Glycine potentiates the action of GABA

Acetyl choline

First chemical neurotransmitter identified was
acetylcholine

Neurotransmitter between axons and striated muscle
at the nueromuscular junction.

Acetylcholine is synthesized in neuronal cytoplasm
from choline and acetyl CoA through the action of
choline acetyl trasferase.



Synthesis and storage

Acetyl CoA is derived from pyruvate metabolism

Choline molecues may be taken up from the blood or
from the synaptic cleft where they have been
produced by acetyl choline hydrolysis or they may be
formed from the degradation of phosphatidyl choline

Acetyl choline is then incorporated into synaptic
vesicles and stored therein.

Release and action:

Release of acetylcholine in response to a action
potential is Ca
2+
dependent.

The released acetyl choline diffuse rapidly across
the synaptic cleft to its receptors on the postsynaptic
membrane (muscle membrane)

Causing opening of the Na
+
channels in the
receptors that permit a flux of actions across the
membranes.

The consequent entry of Na
+
results in depolarizing
the muscle membrane and action potential
generated is transmitted along the fibre, resulting in
contraction of the muscle.



Reuptake and degradation:

Once released acetylcholine must be removed rapidly
in order to allow repolarization to take place.

When the channel closes the acetyl choline
dissociates and is hydrolyzed by acetyl
cholinesterase.


This enzyme is present in high amounts in the synaptic
space.

Acetyl choline may also be hydrolysed by non specific
esterases called pseudo choline esterase which
occurs in many tissues and in plasma.

The choline released by the hydrolysis in the synaptic
cleft is recycled into the nerve terminal by an active
transport mechanism.

Here it is used for resynthesis of acetyl choline.
Nitric Oxide

Nitric oxide is simple gas with free radical
properties but identified as a neurotransmitter.

At low concentration nitric oxide carries nerve
impulses from one neuron to another.

Nitric oxide synthesized in synapses and used
immediately.



Nitric oxide half life is few seconds.
Synthesis of Nitric Oxide
DISORDERS
1. Defect in release of acetyl choline.
Ex: Eaton Lambert Myasthenic Syndrome

2. Neuromuscular Disorder.
Ex: Myasthenia Gravis (AChR antibodies)

3. Excess release.(Norepinephrine ,Epinephrine)
Ex: Phaeochromocytoma

4. Decreased Synthesis.(Dopamine)
Ex: Parkinsons Disease.

5. Bipolar Disorders.(serotonin)
Histamine

It is found in hypothalamus

Histamine is synthesized from histidine by
decarboxylation.

Histamine controls release of pituitary hormones.
Plays a role in sleep awake cycles and food intake
(apetite)