NEUROTRANSMITTERSNEUROTRANSMITTERS

M.Prasad NaiduMSc 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. GABA2. Serotonin3. Acetyl choline4. Catecholamines

DopaNorepinephrineEpinephrine

5. Glycine6. Glutamate

Miscellaneous:

Nitric oxideTaurineHistamineAspartate

Name of the neurotransmitter

Excitatory Inhibitory

1. GABA ----- Inhibitory

2. Catecholamines Excitatory -----

3. Glycine --- Inhibitory

4. Glutamate Excitatory ----

5. Acetyl choline Excitatory -----

6. Serotonin

GABAGABAγ – amino butyric acidSynthesized from A.A L- glutamate by

decarboxylation.

Glutamate decarboxylaseGlutamate GABA

PLPCO2

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

GlutamateNon essential AminoacidExcitatory 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 , Huntington’s 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

OxidaseAcetalyse

Methyal transferase

Serotonin

Serotonin is involved in mood changes SleepAppetite and Temperature regulationIncreases 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 Ca2+ 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 OxideNitric OxideNitric 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

DISORDERSDISORDERS1. 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: Parkinson’s Disease.

5. Bipolar Disorders.(serotonin)

HistamineHistamine

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)