NEUROTRANSMITTERS

Dr Fawzia ALRoug, MBBS, Master, Ph.D

Assistant Professor, Department of
Physiology, College of Medicine, King
Khalid University Hospital, Riyadh, Saudi
Arabia
 NEUROTRANSMITTERS
DEFINITION: Are chemical transducers
which are released by electrical impulse
into the synaptic cleft from presynaptic
membrane from synaptic vesicles. It then
diffuse to the postsynaptic membrane and
react and activate the receptors present
leading to initiation of new electrical
signals.

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 Type of Cells
Neuron
Glia cell

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Neurotransmitter and Receptors

Synaptic transmission: The release of neurotransmitter by a presynaptic

cell and the detection and response of the neurotransmitter by the
postsynaptic cell

Objective of these lectures: to learn the specific mechanisms of the

principal neurotransmitters, to introduce basic neuropharmacology.
Touch on physiological role now, explore in later lectures in more depth.

Classification of neurotransmission

Fast neurotransmission
Neurotransmitter directly activates ligand-gated ion channel receptor

Neuromodulation
Neurotransmitter binds to G-protein coupled receptor to activate a
chemical signaling cascade
 Discovery of neurotransmitters
Loewi, 1921
frog hearts in saline
solution
Stimulation of vagus nerve
results in lower heart rate
gave long vagal nerve
stimulation
Heart #2:
Exposed to saline solution
6
from
Fig 8.1, Zigmond Fundamental Neuroscience
heart #1
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Survey of the major neurotransmitters
 A word about classifying neurotransmitters
Some neurotransmitters have fast and neuromodulatory modes
of function, some exclusively one type or the other

Fast mode: ion channel receptors Modulatory mode: G-protein coupled receptors
(ionotropic receptors) (metabotropic receptors)
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Fate of neurotransmitters
Are as ,
1. It is consumed ( broken down or used
up) at postsynaptic membrane leading to
action potential generation.
2. Degraded by enzymes present in
synaptic cleft.
3. Reuptake mechanism( reutilization) this
is the most common fate.
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Types of responses on
postsynaptic membrane
Excitatory postsynaptic potential (EPSPs)
It is caused by depolarization.
Inhibitory Postsynaptic potential (IPSPs)
It is caused by hyperpolarization.

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Fast & Slow Postsynaptic potentials
Fast EPSPs & IPSPs work through ligand
gated ion channels.eg. Nicotinic
receptors(at the level of neuromuscular
junction)
Slow EPSPs & IPSPs are produced by
multi step process involving G protein
eg. Muscarinic receptors ( at the level of
autonomic gangila)

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 Acetyl Choline Receptors

Nicotinic
1 Found at:
i. Neuromuscular junction of
skeletal muscle
ii. Postganglionic neurons of
parasympathetic nervous
system.
iii. Ventral tegmental area.
Muscarinic
i. Glands
ii. Neuromuscular junctions of
cardiac and smooth muscle.
iii. Postganglionic neurons of
sympathetic nervous system.

2 Agonist Nicotine Muscarine ( a toxin produced by

certain mushroom)

3 Antagonist Curare ( paralyses skeletal Atropine

muscle)
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MAO=monoamine oxidase ,COMT=catechole-o-methyle-transferase
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Formation of serotonin =5-HT
Hydroxy tryptamine
HIAA=hydroxyindoleacetic acid

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Synthesis of neurotransmitters and their precursors. The amino acid tyrosine is the precursor of dopamine,norepinephrine and
epinephrine.Tryptophan is the precursor of serotonin (5-hydroxytryptamine), and histamine derives from the amino acid histidine.
Choline, an amino alcohol is the precursor of acetylcholine, and the common amino acid, glutamic acid, is the precursor of the
GABA.
Neurotransmitters
Heales, Simon J.R., Medical Biochemistry, Chapter 41.1, 551-563

Copyright 2014 2014, Elsevier Limited. All rights reserved.

 Histamine
Histamine forming cells are in posterior
hypothalamus also found in gastric mucosa and
in mast cells.
Formed by decarboxylation of amino acid
histidine with the help of enzyme histaminase.
Three known types of histamine receptors in
found e.g. H1, H2, H3.

H3 receptors are presynaptic. Its function in brain

is not very certain. Its main function is that it is
excitatory.
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 Glycine
It is simplest of all aminoacids, consisting
of amino group and a carboxyl group
attached to a carbon atom
H+

H3 N+ C H+

Coo-

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Glycine..
Its an inhibitory neurotransmitter.
It binds to a receptor which makes the
post synaptic membrane more permeable
to Cl- Ion and cause hyperpolarization
(inhibition).
The glycine receptor is primarily found in
the ventral part of the spinal cord.
Strychnine is glycine antagonist.

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 Glutamic acid
It is the most commonly found neurotransmitter
in the brain.
It is always excitatory.
Glutamate is formed during Krebs cycle for
ketoglutarate.
Glutamate is carried into astrocytes where it is
converted to glutamine and passed on to
glutaminergic neurones.
Glutamate is neurotoxic while glutamine is not.
There are two types of receptors e.g.
metabotropic and iontropic receptors.

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NMDA =N methyl-D-aspartate receptors, when glutamate & glycine bind to receptor ion channels open,
Mg block channels

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 Gamma Aminobutyric acid
(GABA)
It is one of the inhibitory neurotransmitter of CNS
and is also found in retina.
It is formed by decarboxylation of glutamate.
The enzyme that catalyzes this reaction is
glutamate decarboxylase(GAD)
There are three types of GABA receptors e.g.
GABAA B & C.
GABA A & B receptors are widely distributed in
CNS.
GABAC are found in retina only.
GABA B are metabotropic (G-protein) in function.
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 Postsynaptic Site of Postsynaptic
Neurotransmitter Derived from Fate Functions
effect synthesis receptor
1.Acetyl choline Excitatory Acetyl co-A + Cholinergic 1.Nicotinic Broken by acetyl Cognitive functions
(Ach) Choline nerve endings 2.Muscarinic cholinesterase e.g. memory
Cholinergic Peripheral action e.g.
pathways of cardiovascular
brainstem system
2. Catecholamines Excitatory in Tyrosine Adrenal Excites both 1.Catabolized to For details refer
i. Epinephrine some but produced in medulla and alpha & inactive product ANS. e.g. fight or
(adrenaline) inhibitory in liver from some CNS beta through COMT & flight, on heart,
other phenylalanine cells receptors MAO in liver BP, gastrointestinal
2.Reuptake into activity etc.
ii.Norepinephrine Excitatory Tyrosine, found Begins inside 1 2
adrenergic nerve Norepinehrine
in pons. axoplasm of 1 2
endings controls attention &
Reticular adrenergic
3.Diffusion away arousal.
formation, locus nerve ending is
from nerve
coerules, completed
endings to body
thalamus, mid- inside the
fluid
brain secretary
vesicles
iii. Dopamine Excitatory Tyrosine CNS, D1 to D5 Same as above Decreased dopamine
concentrated in receptor in parkinsons
basal ganglia disease.
and dopamine Increased dopamine
pathways e.g. concentration causes
nigrostriatal, schizophrenia
mesocorticolim
bic and tubero-
hypophyseal
pathway

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 Postsynaptic Site of Postsynaptic
Neurotransmitter Derived from Fate Functions
effect synthesis receptor
3. serotonin Excitatory Tryptophan CNS, Gut 5-HT1 to 5-HT Inactivated by MAO Mood control, sleep,
(5HT) (chromaffin 7 to form 5- pain feeling,
cells) Platelets 5-HT 2 A hydroxyindoleacetic temperature, BP, &
& retina receptor mediate acid(5-HIAA) in hormonal activity
platelet pineal body it is
aggregation & converted to
smooth muscle melatonin
contraction
4. Histamine Excitatory Histidine Hypothalamus Three types H1, Enzyme diamine Arousal, pain
H2 ,H3 receptors oxidase threshold, blood
found in (histaminase) cause pressure, blood flow
peripheral tissues breakdown control, gut
& the brain secretion, allergic
reaction (involved in
sensation of itch)
5. Glutamate Excitatory By reductive Brain & spinal Ionotropic and It is cleared from the Long term
75% of amination of cord e.g. metabotropic brain ECF by Na + potentiation
excitatory Krebs cycle hippocampus receptors. dependent uptake involved in memory
transmission intermediate Three types of system in neurons and learning by
in the brain ketoglutarate. ionotropic and neuroglia. causing Ca++ influx.
receptors e.g.
NMDA, AMPA
and kainate
receptors.

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 Postsynaptic Site of Postsynaptic
Neurotransmitter Derived from Fate Functions
effect synthesis receptor

Aspartate & Glycine form an excitatory /

6. Aspartate Excitatory Acidic amines Spinal cord Spinal cord
inhibitory pair in the ventral spinal cord

GABA A
increases the Cl GABA A causes
- conductance, hyperpolarization
Decarboxylation GABA B is (inhibition)
of glutamate by metabotropic Anxiolytic drugs like
Metabolized by
7. Gama amino Major glutamate works with G benzodiazepine cause
transamination to
butyric inhibitory decarboxylase CNS protein GABA increase in Cl- entry
succinate in the citric
acid(GABA) mediator (GAD) by transaminase into the cell & cause
acid cycle.
GABAergic catalyzes. soothing effects.
neuron. GABA C GABA B cause
found increase conductance
exclusively in of K+ into the cell.
the retina.

Deactivated in the
Is simple amino Glycine receptor Glycine is inhibitory
synapse by simple
acid having makes transmitted found in
process of
amino group and postsynaptic the ventral spinal
8. Glycine Inhibitory Spinal cord reabsorbtion by active
a carboxyl group membrane more cord. It is inhibitory
transport back into
attached to a permeable to Cl- transmitter to
the presynaptic
carbon atom ion. Renshaw cells.
membrane

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 RECEPTORS DYSFUNCTION
1. Presynaptic effect
i) Botulinum toxin: Its an exotoxin that binds
to the presynaptic membrane and
prevents the release of Ach resulting in
weakness and reduction of tone. It is
used to control dystonia in which body
shows overactive muscular activity.

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ii) Lumbert Eaton syndrome
Antibodies directed against Ca++ channels
located in presynaptic terminals and
interfere with transmitter release causing
weakness.
iii)Neuromyotonia
Patient complains of muscle spasm and
stiffness resulting in continuous motor
activity in the muscle. It is cased by
antibody directed against the presynaptic
voltage gated K+ channel so that the nerve
terminal is always in a state of
depolarization 36
2. Effects at Postsynaptic level:
i) Curare binds to the acetylcholine
receptor (AchR) and prevents Ach from
acting on it and so that it induces
paralysis.
ii) Myasthenia gravis: is caused by an
antibody against the Ach receptors and
Ach receptors are reduced hence the
Ach released has few Ach receptor
available to work and patients complain
of weakness that increases with
exercise. 37
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 Synaptic strength
Can be facilitated like long term
potentiation.
Can be depressed ( inhibited) by long-term
depression.

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Classification of Neurotransmitters
Amines
A. Acetyl choline (Ach)
B. Monoamines
Catecholamines
Epinephrine
Nor epinephrine
Dopamine (Substantia nigra, sympathetic
ganglia)

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 Serotonin ( hypothalamus, cerebellum,
spinal cord, retina)
Histamine ( Hypothalamus)
Amino acids:
I. Excitatory eg. Glutamate ( cortex,
brainstem)
- Aspartate (visual cortex)
II. Inhibitory eg. Gamma amino butaric
acid GABA cerebrum, cerebellum
presynaptic inhibitory neurone in retina
- Glycine spinal cord.
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III. Purine derivatives
eg. Adinosine & ATP.
IV. Polypeptides ( a very long list of names)
eg. Enkephaline, hormones ( VIP etc)
( refer to the list in Ganong 21st edition pg.97)
V. Nonsynaptic transmitters
eg. Gases, nitric oxide & cabon mono
oxide.

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Dopamine: Reward Reinforcement and Feeding Behaviors

Overall control of feeding behavior is a complex process involving

several well dened neural circuits. These circuits consist of
interactions between the brainstem and the hypothalamus as well as
interactions between the gut and the hypothalamus. For detailed
information on the latter go to the Gut-Brain Interrelationships page.
The control of feeding behavior also involves overlapping processes
such as motivational drive, satiety and the anticipation of food. A major
neurotransmitter involved in the coordination and reinforcement of
these reward processes is dopamine. Indeed, every known type of
reward, including food, results in increased levels of dopamine in the
brain. Although the cell bodies of dopaminergic neurons are confined to
only a few areas of the brain, these neurons send projections to
numerous areas including those involved in the regulation of feeding
behaviors such as the hypothalamus.

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Dopamine mediates the motivational and rewarding aspects of food
seeking behavior via specific dopaminergic projections from the ventral
tegmental area (VTA) to the nucleus acumbens (NAc). The VTA is the
origin of the dopaminergic cell bodies and the NAc is a brain region in
the basal forebrain that sends projections to the basal ganglia situated at
the base of the forebrain. The NAc is involved in reinforced learning,
reward, pleasure, addiction, fear, aggression, and impulsivity. The
reward pathways involving dopamine are also referred to as the
mesolimbic or mesocorticolimbic system which also sends projections to
the medial prefrontal cortex, hippocampus and amygdala. The
mesolimbic dopamineric circuits are involved in the motivation to earn
food rewards but not for the triggering of actual food consumption.

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