NEUROTRANSMITTERS

INTRODUCTIO
N
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
A schematic representation of a chemical
synapse
Axo
n

Pre synaptic Vesicles

(containing
knob neurotransmitter
s)
Synaptic
Post synaptic cleft
Receptors
knob

Receiving
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.
TYPES OF
NEUROTRANSMITTERS

EXCITATOR INHIBITOR BOT

Y Y H
Glycin Acetylcholi
Glutamate e ne

GAB Nor
Aspartate A epinephrine
Serotoni
n
Nitric oxide
Dopamin
e
Receptors of neurotransmitters
A- Ionotropic Receptors

1. Work very fast; important role in fast neurotransmission

2. Each is made of several subunits (together form the complete receptor)
3. At center of receptors is channel or pore to allow flow of neurotransmitter
4. At rest - receptor channels is closed
5. When neurotransmitter bind -- channel immediately opens
6. When ligand leaves binding site -- channel quickly closes
B- Metabotropic Receptors

1. Work more slowly than ionotropic receptors

2. Comprise a single protein subunit, winding cell membrane seven times
(transmembrane domains)
3. They do not possess a channel or pore
Neurotransmitters are .1
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.
 Steps in neurotransmitter
:Synthesis:
processing are
Neurotransmitters are synthesized
by the
enzymatic transformation of
precursors.

They areStorage: They presynaptic

released from
Release are packaged inside synaptic
terminal
vesicles.
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
ACETYLCHOLINE (ACH)
 Acetylcholine was the first neurotransmitter to be
discovered.
 1921 by a German biologist named Otto Loewi.

 -Uses choline as a precursor - cholinergic

neurotransmitter.
 -Used by the Autonomic Nervous System, 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. Acetylcholine is
decreased in both concentration and function in
patients with Alzheimer's disease.
 Too much: muscle contractions- e.g.
organophosphorus (OP) poisoning
 Acetylcholine
Synthesis Removal
Acetyl CoA CoA Acetate
+ + Ach +
Choline Acetyltransferase Acetylcholine
Choline (ChAT) ACh Esterase (AChE) Choline

• 2 receptor types
• Nicotinic (ionotropic): Excitatory;
found predominately on neuromuscular
junctions
• Muscarinic (metabotropic) :Both
excitatory and Inhibitory; found
predominately in brain
 Monoamines
They are neurotransmitters and neuromodulators that
contain one amino group connected to an aromatic ring by a
two-carbon chain (such as -CH2-CH2-).

• Catecholamines • Indolamines
Dopamine - DA Serotonin - 5-HT
– Dopaminergic – Serotonergic
Norepinephrine - NE
– Noradrenergic
Epinephrine - E
– Adrenergic ~
Monoamines (DA, NE, 5-HT)
• Modulatory (can have both
excitatory and inhibitory
effects- varies by receptor)
• Recycled by reuptake
transporter
• Excess NT in terminal broken
down by
– monoamine oxidase (MAO)
– catechol-O-methyltranferase -
COMT
 Dopamine (DA)
Tyrosine L-DOPA DA
Biosynthesis: Tyrosine DOPA
Hydroxylase Decarboxylase

• Dopamine reuptake transporter (DAT)

• 5 receptor types (D1–D5, all metabotropic)
• Too little: Parkinson's disease:
• Treatment: Increase available DA via L-Dopa
• Too much: schizophrenia
• Treatment: Reduce available DA via
antidopaminergics/antipsychotics
 Norepinephrine
• Generally excitatory behavioral effects
DA NE
• Biosynthesis: Dopamine
Beta-hydroxylase
• Many receptor types (metabotropic)
• 1, 1-2 (postsynaptic, excitatory) 2 (autoreceptor, inhibitory)
• Norepinephrine is strongly associated with bringing our nervous
systems into "high alert."
• It increases heart rate and blood pressure.
• It is also important for forming memories.
Catabolism
• It occurs through the actions of catecholamine-O-
methyltransferase, (COMT) and monoamine oxidase,
(MAO). Both of these enzymes are widely distributed
throughout the body. However, COMT is not found in
nerve endings as is MAO.
 Serotonin (5-HT)
• Varying excitatory and inhibitory behavioral effects
• Biosynthesis:
Tryptophan 5-HTP 5-HT
Tryptophan 5-HT
Hydroxylase Decarboxylase

• At least 14 receptor types, all metabotropic and postsynaptic

except:
• 5-HT1A,B,D (autoreceptors) – found in CNS
• 5-HT3 (inhibitory, ionotropic) – found in the intestines
• Too little is linked to depression and sleep disorders
• Too much: Serotonin syndrome: confusion, twitching and trembling,
dilated pupils, shivering, headache, sweating and diarrhea., irregular
and fast heartbeat
GLUTAMAT
E
 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 formedfrom α – ketoglutarate,

an
intermediate of Kreb’s cycle.
 GABA (Gamma Aminobutyric Acid)
• Principal Inhibitory NT
• Biosynthesis:
Glu Glutamic Acid
GABA
Decarboxylase (GAD)
and B6
• Removed by reuptake
• 2 receptor types
• GABAA GABAC (ionotropic; Cl- channel)
• GABAB (metabotropic)
If GABA is lacking in certain parts of the
brain, epilepsy results.
 Neuropeptides
• Low concentration in brain (picomolar)
• Large vesicles
• Co-localized with other transmitters
• Modulatory functions
• Mostly inhibitory
• Virtually all metabotropic
• Slow acting, long duration
• Examples: Enkephalins, Endorphins, Oxytocin,
Vasopressin, Opioids
 Endorphins

• Morphine and heroin are agonists that bind to

receptor sites, thereby increasing endorphin
activity
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.
DISEASES ASSOCIATED WITH
NEUROTRANSMITTERS
NEUROTRANSMITTER DISEASE
 Acetylcholine  Alzheimer’
s
 Dopamine
 Parkinson’
s disease
 GABA  Schizophr
Epilepsy
enia
 Serotonin  Migraine
s
 Depressi
on
  Migrain
Glutamate e
 stroke
RECENT
DEVELOPMENTS
 A team of scientists from University of
Barcelona in 2011, has discovered that D-
aspartic acid (D-Asp) is a novel
neurotransmitter that could potentially be
used in the fight against neurological
diseases such as Parkinson's and
schizophrenia.

 According to a new study by researchers

at the Ohio State University
Comprehensive Cancer Center in 2011,
doses of a neurotransmitter dopamine
might offer a way to boost the
effectiveness of anticancer drugs and