NEURO

TRANSMITTER
SITI ANNISA DEVI TRUSDA
OVERVIEW
• DEFINITION
• CLASSIFICATION
• SYNTHESIS
• RECEPTORS
• DEGRADATION AND REUPTAKE
• MECHANISM OF ACTION
DEFINITION
 Neurotransmitters
• = chemicals that are used to relay, amplify and
modulate electrical signals between a neuron and
another cell.
• Talking about NT - if it respects the following
conditions:
• It is synthesized endogenously, that is, within the presynaptic
neuron
• It is available in sufficient quantity in the presynaptic neuron
to exert an effect on the postsynaptic neuron
• Externally administered, it must mimic the endogenously-
released substance
• A biochemical mechanism for inactivation must be present
 Neurotransmitter
Criteria
1. Identity
2. Synthesis
Cell has precursors and enzymes
necessary for synthesis
 Neurotransmitter
Criteria
1. Identity
2. Synthesis
3. Release
Must be released from terminals;
(collect substance from cleft
after nerve stimulation)
 Neurotransmitter
Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
Blockade of n.t. action by receptor
antagonists
Applicaton of suspected n.t.
mimics action of nerve stimulation
 Neurotransmitter
Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
5. Inactivation
Inactivation mechanism
enzymatic degradation
reuptake
 Neurotransmitter
Criteria
1. Identity
2. Synthesis
3. Release
4. Receptors
5. Inactivation
Inactivation mechanism
enzymatic degradation
reuptake
CLASSIFICATION
 Types of neurotransmitters
 Monoamines
• Biogenic amines  Catecholamines (from

• Acetylcholine (Ach) phenylalanine and tyrosine)

• Amino acids  Dopamine (DA)

• Aspartate  Norepinephrine (NE)

• Glutamate (Glu)  Epinephrine (Epi)

• γ-Aminobutyric acid  From tryptophan:

(GABA)  Serotonin (5-HT)

• Glycine (Gly)  Melatonin (Mel)

 From histidine:

 Histamine (H)
 Neurotransmitters found in the nervous system
EXCITATORY INHIBITORY
Acetylcholine GABA
Aspartate Glycine
Dopamine
Histamine
Norepinephrine
Epinephrine
Glutamate
Serotonin 12
SYNTHESIS OF
NEUROTRANSMITTER
BIOGENIC AMIN : ACETYLCHOLINE
 Acetylcholine
 First neurotransmitter found (1921)
 In PNS and CNS
 Acetylcholine is synthesized in certain neurons by
the enzyme choline acetyltransferase from the
compounds choline and acetyl-CoA.
 shortage of acetylcholine in the brain has been
associated with Alzheimer's disease
 ACH receptors
 nicotinic acetylcholine receptors (ionotropic) are particularly
responsive to nicotine. Located in the CNS and
preganglionic parts of autonomic system.
 muscarinic acetylcholine receptors (metabotropic) are
particularly responsive to muscarine. Located in the CNS
and postganglionic parts of autonomic system.
AMINO ACIDS
Amino Acid Transmitters
Excitatory Amino Acid
Glutamic Acid, or Glutamate

Inhibitory Amino Acids

Gamma Aminobutyric Acid (GABA)
Glutamic Acid
Decarboxylase (GAD)
Glutamic Acid GABA

Glycine
 Glutamate (Glutamic acid)
 Most abundant excitatory neurotransmitter in the nervous
system.
 In excess, glutamic acid triggers a process called
excitotoxicity, causing neuronal damage and eventual cell
death, particularly when NMDA receptors are activated
(epilepsy).
 It’s overstimulation occurs as part of the ischemic cascade
and is associated with diseases like amyotrophic lateral
sclerosis and Alzheimer's disease.
 Receptors:
 Ionotropic – NMDA; non-NMDA (AMPA, Kainate)
 Metabotropic
Glutamate Receptor Subtypes
NMDA receptor binding sites
 Glutamate
non-NMDA receptors NMDA receptors

Na+ channels Ca2+ channels

open open
removes (Mg2+ blockade)
depolarization blockade
Ca2+ enters
when Mg2+
is removed

postsynaptic Ca2+dependent
effects K+ channels
(learning) open

reinstates blockade
repolarization
a. Non-NMDA Na+ channels open, Na+
enters and depolarizes membrane
b. Mg2+ blockade of NMDA Ca2+ channels
removed by membrane depolarization;
Ca2+ enters
c. Ca2+ dependent K+ channels open;
membrane repolarized
d. Mg2+ blockade reinstated

a b c d
 Gamma-aminobutyric acid
(GABA)

 Most important inhibitory neurotransmitter in the

CNS.
 Acts as a transmitter, the inhibition results from a
hyperpolarization of the transmembrane potential
of the inhibited neuron.
 Receptors:
 GABA A – ionotropic – Cl-
 GABA B – metabotropic - via G-proteins to potassium
channels
 GABA C – as GABA A (Cl- ) but slow response
GABA receptor binding sites
MONOAMINES
 Monoamines
single amine (NH2) group
Catecholamines (CAs)
dopamine (DA)
norepinephrine (NE, noradrenaline)
epinephrine (EPI, adrenaline)

Indoleamines
serotonin (5-hydroxy tryptamine, 5-HT)
 Functions of
Monoaminergic Systems
“State” phenomena
sleep and arousal
hunger
mood
 Characteristics of
Monoaminergic Systems
Diffuse distribution of targets
Fine, unmyelinated axons
Metabotropic synapses
Catecholamine synthesis
 Dopamine

 In the brain, dopamine functions as a

neurotransmitter
 DA is also a neurohormone released by the
hypothalamus.
 Functions of dopamine in the brain:
 Role in movement (basal ganglia)
 Role in cognition and frontal cortex function (frontal lobe
and prefrontal area)
 Role in pleasure and motivation (nucleus accumbens,
striatum)
 Pathophysiology - psychosis and schizophrenia
 Therapeutic use – L-DOPA – Parkinson’s disease
 Serotonin

 In the CNS - important role in the regulation of

mood, sleep, emesis (vomiting), sexuality and
appetite.
 5-HT has been thought to play a part in many
disorders, notably as part of the biochemistry of
depression, migraine, bipolar disorder and anxiety.
 A variety of psychiatric and neurological
medications affect serotonin levels:
 Antidepressants
 Antiemetics
Serotonin synthesis
 Peptide
Neurotransmitters
(Often serve hormonal functions
as well)
Substance P (P for “Peptide”)
Principal somatosensory transmitter
First peptide transmitter discovered
Gut hormones
e.g. angiotensin
neuropeptide Y
cholecystokinin
Releasing factors for hormones
e.g. tryrotropin releasing hormone
somatotrophin, somatostatin
corticotropin
Opiates
Enkephalins, Endorphins
 Opiates
 Endorphin
 Enkephalin
 Enkephalins,pentapeptides containing the
consensus Tyr-Gly-Gly-Phe-Xaa
sequence, are the smallest of the
molecules with pain killing or opiate
activity.
Structure of enkephalin
 Found in the thalamus
 some parts of the spinal cord that transmit
pain impulses.
 In the spinal cord, enkephalins inhibit
painful sensations by reacting with specific
receptor sites on the sensory nerve
endings.
 Nerve endings of the central nervous
system (CNS) and the adrenal medulla
release these naturally occurring
morphine-like substances.
 Enkephalins bind to opiate receptors and
release controlled levels of pain.
 Leu-enkephalin is an endogenous agonist
for the receptors that are stimulated by
opiate alkaloids. It has multiple effects on
the CNS, including the neuroendocrine
hypothalamus.
 Leu-enkephalin also controls gonadal
function.
 Met-enkephalin is involved in phenomena
associated with modulated pain
perception, regulation of memory and
emotional conditions, food and liquid
consumption and regulation of
immunological system.
 It also has an impact on the digestive
system motility, gastric as well as in
pancreatic secretion and metabolism of
carbohydrates.
Diffusible Gases
Nitric Oxide (NO)
Nitric Oxide
Synthase (NOS)
Arginine NO + Citrulline

Carbon Monoxide (CO)

Heme Oxygenase

Heme CO + biliverdin
 Functions of
Diffusible Gas
Neurotransmitters
regulate blood flow
cerebral
peripheral (e.g. penis)
retrograde messenger
Hebb’s postulate of learning
DEGRADATION AND REUPTAKE
Inactivation of the Neurotransmitter
1. Reuptake
2. Enzymes that degrade the NT (enzymatic
degradation)
NTs are sequestered back into vesicles, which have
been formed through pinocytosis (i.e. pinching off
of the cell membrane to form vesicles).
___________________________________
Note: although EPSPs leading to an Action
Potential seem to get all the attention, our
neurophysiology is always in a balance between
EPSPs and IPSPs.
RECEPTORS
MECHANISM OF ACTION
• Metabotropic
• Ionotropic