INTRODUCTION AND CLASSIFICATION OF

NEUROTRANSMITTERS
LEARNING OBJECTIVES:

By the end of this lecture, the students should know:

The different types of Neurotransmitters in CNS.
Classification of Neurotransmitters
Mechanism of action of various types of Neurotransmitters
The neurotransmitter receptors

NEUROTRANSMITTERS
Neurotransmitters are the
chemicals responsible for signal transmission
between the individual neurons

Most neurons make two or more

neurotransmitters, which are released
at different stimulation frequencies

50 or more neurotransmitters
have been identified
Classified by chemical structure
and by function
CRITERIA TO CLASSIFY A BIOCHEMICAL SUBSTANCE AS
NEUROTRANSMITTER:

Substance must be present in the pre-synaptic nerve terminal

and packaged into synaptic vesicles
The substance must be released from the nerve terminal upon
arrival of action potential or depolarization of presynaptic
membrane
Specific receptors must be present on the post synaptic
membrane for the substance

LIFE CYCLE OF A NEUROTRANSMITTER

1) Synthesis of the transmitter

2) Packaging and storage in

Synaptic vesicles

3) If necessary, transport from

the site of synthesis to the site
of release from the nerve terminal

4) Release in response to an
action potential

5) Binding to postsynaptic
receptor proteins

6) Termination of action by diffusion,

destruction, or reuptake into cells.
CHEMICAL CLASSIFICATION OF NEUROTRANSMITTERS:
1. Acetylcholine
2. Biogenic Amines
Catecholamines: Dopamine, norepinephrine (NE), and
epinephrine
Indolamines
Serotonin and histamine (5-Hydroxytryptamine or 5-HT)
3. Amino Acids
GABAGamma ()-aminobutyric acid
Glycine
Aspartate
Glutamate
4. Neuropeptides
Substance P
Endorphins and Enkephalins
Somatostatin, gastrin, cholecystokinin, oxytocin, vasopressin,
Leutinizing hormone releasing hormone (LHRH)
5. Purines
Adenosine
ATP
6. Gases and Lipids
Nitric Oxide (NO)
Carbonmonooxide (CO)
Cannabinoids

FUNCTIONAL CLASSIFICATION OF
NEUROTRANSMITTERS:
1. Excitatory Neurotransmitter
2. Inhibitory Neurotransmitter
ACETYLCHOLINE (ACH)

Acetylcholine (Ach) was the first neurotransmitter to be

identified
It is the most abundant neurotransmitter in the brain
Released at neuromuscular junctions and some ANS neurons
Synthesized by enzyme choline acetyltransferase
Degraded by the enzyme acetylcholinesterase (AChE)

CATECHOLAMINES
Catecholamines-Dopamine, norepinephrine (NE), and epinephrine
are synthesized from Tyrosine
Is involved in reward-pleasure and learning
Dopamine is the principle neurotransmitter involved in Addiction
pathway

SEROTONIN
Broadly distributed in the brain, derived from Tryptophan
involved in sleep, dreaming, hunger and arousal
Play roles in emotional behaviors and the biological clock
Depletion of serotonin in brain leads to depression
GABA
GABAGamma ()-aminobutyric acid is the
major inhibitory neurotransmitter in CNS
synthesized from decarboxylation of
Glutamate
involved in regulating anxiety
may be related to eating or sleep disorders

ENDORPHINS, ENKEPHALINS AND SUBSTANCE P

Substance P is the mediator of pain signals
Endorphins and Enkephalins act as natural opiates; reduce pain
perception
They also depress physical functions
like breathing and may produce physical
dependence

PURINES SUCH AS ATP

Purines such as ATP:
Act in both the CNS and PNS
Produce fast or slow responses
Induce Ca2+ influx in astrocytes
Provoke pain sensation

NITRIC OXIDE (NO)

Nitric oxide (NO)
Synthesized on demand
Activates the intracellular receptor
guanylyl cyclase to cyclic GMP
Involved in learning and memory

ENDOCANNABINOIDS
Endocannabinoids
Lipid soluble; synthesized on demand from membrane lipids
Bind with G proteincoupled receptors in the brain
Involved in learning and memory
FUNCTIONAL CLASSIFICATION OF NEUROTRANSMITTERS
Neurotransmitter effects may be excitatory (depolarizing) and/or
inhibitory (hyperpolarizing)
Determined by the receptor type of the postsynaptic neuron
GABA and glycine are usually inhibitory
Glutamate is usually excitatory
Acetylcholine-Excitatory at neuromuscular junctions in skeletal
muscle

NEUROTRANSMITTER ACTIONS
Direct action
Neurotransmitter binds to channel-linked receptor and opens ion
channels
Promotes rapid responses
Examples: ACh and amino acids

Indirect action
Neurotransmitter binds to a G protein-linked receptor and acts
through an intracellular second messenger
Promotes long-lasting effects
Examples: biogenic amines, neuropeptides, and dissolved gases

NEUROTRANSMITTER RECEPTORS
Types
1. Channel-linked receptors
2. G protein-linked receptors
Channel-Linked (Ionotropic) Receptors
Ligand-gated ion channels
Action is immediate and brief
Excitatory receptors are channels for small cations
Na+ influx contributes most to depolarization
Inhibitory receptors allow Cl influx or K+ efflux that causes
hyperpolarization

G Protein-Linked (Metabotropic) Receptors

Transmembrane protein complexes
Responses are indirect, slow, complex, and often prolonged
and widespread
Examples: muscarinic ACh receptors and those that bind
biogenic amines and neuropeptides

G Protein-Linked Receptors: Mechanism

Neurotransmitter binds to G proteinlinked receptor
G protein is activated
Activated G protein controls production of second messengers,
e.g., cyclic AMP, cyclic GMP, diacylglycerol or Ca2+
Second messengers:
Open or close ion channels
Activate kinase enzymes
Phosphorylate channel proteins
Activate genes and induce protein synthesis