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

GABA —Gamma ()-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
• GABA —Gamma ()-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 Ca
2+ 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 protein –coupled 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 protein
–linked receptor
• G protein is activated
• Activated G protein controls production of second messengers, e.g., cyclic AMP, cyclic GMP, diacylglycerol or Ca
2+
Second messengers:
• Open or close ion channels
• Activate kinase enzymes
• Phosphorylate channel proteins
• Activate genes and induce protein synthesis