INTRODUCTION TO

NEUROTRANSMITTERS

BY: Mudasir Maqbool

Mohmad Amin Dar
INTRODUCTION
 Neurotransmitters are chemical messengers that
transmit signals from a neuron to a target cell across
a synapse.

 Target cell may be a neuron or some other kind of cell like

a muscle or gland cell.

 Necessary for rapid communication in synapse.

 Neurotransmitters are packaged into synaptic vesicles -

presynaptic side of a synapse.
Illustration of the major elements in chemical synaptic transmission.
A schematic representation of a chemical synapse

Axon

Pre synaptic Vesicles (containing

neurotransmitters)
knob Synaptic cleft
Receptors

Post synaptic
Receiving
knob neuron
 PROPERTIES OF
NEUROTRANSMITTERS
1) Synthesized in the presynaptic neuron

2) Localized to vesicles in the presynaptic neuron

3) Released from the presynaptic neuron under

physiological condition

4) Rapidly removed from the synaptic cleft by uptake

or degradation

5) Presence of receptor on the post-synaptic neuron.

6) Binding to the receptor elicits a biological

response
TYPES OF NEUROTRANSMITTERS

EXCITATORY INHIBITORY BOTH

Glycine Acetylcholine
Glutamate

GABA Nor epinephrine

Aspartate
Serotonin

Nitric oxide
Dopamine
 Table 1. Classes of CNS Transmitters

Neurotransmitter % of Brain Function Primary

Synapses Concentration Receptor Class

Monoamines 2-5 nmol/mg Slow change in GPCRs

Catecholamines: DA, NE, protein excitability (secs)
EPI (low)
Indoleamines: serotonin
(5-HT)

Acetylcholine (ACh) 5-10 nmol/mg Slow change in GPCRs

protein excitability (secs)
(low)
Amino acids μmol/mg Rapid inhibition Ion channels
Inhibitory: GABA, glycine 15-20 protein (msecs)
(high)
Excitatory: Glutamate,
aspartate 75-80 μmol/mg Rapid excitation Ion channels
protein (msecs)
(high)

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 Table 1. Classes of CNS Transmitters

Neurotransmitter % of Brain Function Primary

Synapses Concentration Receptor Class

Monoamines 2-5 nmol/mg Slow change in GPCRs

Catecholamines: DA, NE, protein excitability (secs)
EPI (low)
Indoleamines: serotonin
(5-HT)

Acetylcholine (ACh) 5-10 nmol/mg Slow change in GPCRs

protein excitability (secs)
(low)
Amino acids μmol/mg Rapid inhibition Ion channels
Inhibitory: GABA, glycine 15-20 protein (msecs)
(high)
Excitatory: Glutamate,
aspartate 75-80 μmol/mg Rapid excitation Ion channels
protein (msecs)
(high)

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 Table 2. Major Neurotransmitter Receptors in the CNS

Neurotransmitter Receptor Subtypes G Protein-Coupled (G) vs.

Ligand-Gated Ion Channel (LG)

DA D1 G
D2 G
D3 G
G
D4 G
D5

NE/EPI α1 G
α2 G
β1 G
G
β2 G
β3

5-HT 5-HT1A G
5-HT1B G
5-HT1D G
G
5-HT2A G
5-HT2B G
5-HT2C LG
5-HT3 G
5-HT4

ACh Muscarinic M1 G
Muscarinic M2 G
Muscarinic M3 G
G
Muscarinic M4 LG
Nicotinic

Glutamate NMDA LG
AMPA LG
Kainate LG
Metabotropic G
10
GABA A LG
B G
ACETYLCHOLINE (ACh)
 Acetylcholine was the first neurotransmitter to be discovered.
 Isolated in 1921 by a German biologist named Otto Loewi.

 Uses choline as a precursor - cholinergic neurotransmitter.

 Used by the Autonomic Nervous System, such as smooth muscles

of the heart, as an inhibitory neurotransmitter.

 Responsible for stimulation of muscles, including the muscles of

the gastro-intestinal system.

 Used everywhere in the brain.

 Related to Alzheimer's Disease.
 DOPAMINE
 Is synthesized in three steps from the amino acid tyrosine.

 Associated with reward mechanisms in brain.

 Generally involved in regulatory motor activity, in mood,

motivation and attention.

 Schizophrenics have too much dopamine.

 Patients with Parkinson's Disease have too little

dopamine.

Dopamine
NOREPINEPHRINE (nor adrenaline)
 Synthesized directly from dopamine.
 Direct precursor to epinepherine.

 It is synthesized in four steps from tyrosine.

 Synthesized within vesicles.

 Norepinephrine is strongly associated with bringing our

nervous systems into "high alert."

 It increases our heart rate and our blood

pressure.
 It is also important for forming memories.

Norepinephrine
 GLUTAMATE
 It is an amino acid

 It the most commonly found

• excitatory neurotransmitter in the brain.

 It is involved in most aspects of normal brain function

including cognition, memory and learning.

 Glutamate is formed from α – ketoglutarate,

an
• intermediate of Kreb’s cycle.
 γ-AMINO BUTYRIC ACID
(GABA)
 Synthesized directly from glutamate.

 GABA is the most important inhibitory neurotransmitter

 Present in high concentrations in the CNS, preventing the

brain from becoming overexcited.

 If GABA is lacking in certain parts of the brain, epilepsy

results.

GABA
SEROTONIN (5-HT)
 Synthesized in two steps from the amino acid
tryptophan

 Regulates attention and other complex cognitive

functions, such as sleep (dreaming), eating, mood,
pain regulation.

 Too little serotonin has been shown to lead to

depression, anger control etc.
 1.Neurotransmitters are
synthesized from precursors
under the influence of enzymes

2. Stored in vesicles
3.Neurotransmitter molecules
that leak from their vesicles are
destroyed by enzymes
4.Action potential cause vesicle
to fuse with synapse and release
neurotransmitters
5.Some of it binds with auto
receptor and inhibit subsequent
neurotransmitter release
6.Rest of it bind to post
synaptic receptors.
7.Released neurotransmitters
are deactivated either by re
uptake or enzyme degradation.
 Steps in neurotransmitter processing are:
Synthesis: Neurotransmitters are synthesized by the
enzymatic transformation of precursors.

Storage: They are packaged inside synaptic vesicles.

Release: •They are released from presynaptic terminal by

exocytosis when calcium enters axon terminal during
an action potential
•Diffuse across the synaptic cleft to the
postsynaptic membrane.

Binding: They bind to receptor proteins.

Inactivation: The neurotransmitter is degraded either by

being broken down enzymatically, or reused by
active reuptake.
MODE OF ACTION OF ACETYLCHOLINE
• When nerve impulse reaches pre synaptic knob Ca
channels open.
• Increased Ca ions fusion of vesicle
Release
presynaptic
to membrane and release of ACh into cleft.

• ACh bind to receptors in post synaptic membrane.

• Ion channels open inflow of Na and K ions
• Depolarisation and formation of action potential.
Binding • Propogation of action potential & contraction of
fibres.

• ACh is hydrolysed by acetyl cholinesterase.

• Choline taken back to presynaptic domain for
Deactivation resynthesis of Ach.
ALCOHOL & NEUROTRANSMITTERS
 It binds directly to receptors for ACh,

serotonin, GABA and glutamate.

 It enhances the effects of the GABA,

which is an inhibitory
neurotransmitter.
◦ Enhancing an inhibitor make things
sluggish.
◦ The neuron activity is diminished-
sedative effects of alcohol.

 Alcohol inhibits glutamate receptor

function.
◦ This causes discoordination, slurred speech, staggering,
memory disruption, and blackout.
 NICOTINE &
NEUROTRANSMITTERS
 Nicotine imitates the action of
ACh & binds to ACh receptor.

 Like acetylcholine, nicotine leads to a burst of

receptor activity.

 Nicotine activates cholinergic neurons in many

different regions throughout your brain
simultaneously.

 This stimulation leads to:

◦ Increased release of glutamate.
◦ Stimulation of cholinergic neurons promotes the
release of dopamine. The production of dopamine
causes feelings of reward and pleasure.
DISEASES ASSOCIATED WITH
NEUROTRANSMITTERS
NEUROTRANSMITTER DISEASE
 Acetylcholine  Alzheimer’s

 Dopamine  Parkinson’s disease

 Schizophrenia

 GABA  Epilepsy

 Serotonin  Migraines
 ADD
 Depression

 Glutamate  Migraine
 stroke