Biochemistry of
Neurotransmitters
Dr. Abdullah A. Osman
Objectives
To define the chemical synapses
To discuss the major classes of molecules that function
as neurotransmitters at chemical synapses
To discuss the structure, origin, function of
neurotransmitters and their receptors
To discuss the effects of neurotransmitters on
postsynaptic cells
To define synaptic transmission
To know the principal action of cholinergic agonists and
antagonists
Neurons and Central nervous System
The nervous system regulates all aspects of bodily
function
The human brain-control center that stores, computates
and transmits information
The human brain contains~ 1012 neurons (nerve cells)-
each forming as many as thousands connections with
other neurons
Millions of neurons regulates contraction of muscle and
secretion of hormones
Function of neurons-to communicate information by two
methods:
“Continued”
A) Electrical signals: process and conduct information
within a cell
B) Chemical signals: transmit information between cells
Type of neurons:
A) Motor neurons-carry information and innervate
muscle cell via axon terminals
B) Sensory neurons-have specialized receptors that
convert stimuli into electrical impulse which passes down
to the cell body, and then to spinal cord or brain
Synapses
Are specialized sites where neurons communicate with
other cells
They transmit signals in only one direction (from axon
terminal to postsynaptic cell)
Two types:
1) Electrical synapses-rare and fast
2) Chemical synapses-common, slow and release
neurotransmitters
The neuromuscular junctions-are junction between the
axon terminal of a neuron and the receiving cell (muscle
cells) and usually called synapse
Typical Mammalian Neuron Structure
Neurons are specialized to produce and utilize different
neurotransmitters-chemicals that act in a paracrine fashion
Membrane Potential
Action potential: neurons and muscle cells generate
electrical signals that are conducted rapidly over long
distances
Resting membrane potential: action potential produced when
there is no active ionic conduction-an equilibrium state exists
Membrane depolarization: a reduction in membrane potential
due to flow of cations into cells
Membrane hyperpolarization: an increase in membrane
potetial due to influx of anions from outside the cells
Exictatory synapse: represents membrane depolarization
Inhibitory synapse: represents membrane hyperpolarization
Neurotransmitters
Transmitter Derived From Site of Synthesis
Molecule
Acetylcholine Choline CNS,
Parasympathetic
nerves
Serotonin Tryptophan CNS
5-hydroxytryptamine
GABA (gamma- Glutamate CNS
amino butyric acid)
Glutamate CNS
Aspartate CNS
Glycine Spinal cord
Histamine Histidine Hypothalamus
Epinephrine Tyrosine Adrenal medulla,
(adrenalin) some CNS cells
Norepinephrine Tyrosine CNS, sympathetic
(noradrenalin) nerves
Dopamine Tyrosine CNS
Adenosine ATP CNS, Peripheral
nerves
Acetylcholine (Ach)
Used within the peripheral nervous system
Synthesized from choline and acetyl CoA in the
axon terminals
Neurons that secrete Ach and receptors that
bind Ach are described as cholinergic
Ach is excitatory at neuromuscular junctions
(NMJs), where it acts directly to open ligand-
gated cation channels
Ach is inhibitory in the autonomic
parasympathetic division, e.g. vagus nerve to
inhibit heart rate
Acetylcholine Biosynthesis
Acetylcholine-Chemical Synapse
Transmission
Acetylcholine (Ach) “continued”
Ach binds to two types of cholinergic receptors: are
ligand-gated cation channels (Na+ and K+)
1) cholinergic nicotinic receptors:
a) found at the NMJs of skeletal muscle cells (only)
b) found on the post-gnglionic neurons of
parasympathetic nervous system and many
neurons in the brain
c) nicotine is an agonist ( hence the name)
d) curare is antagonist (its ability to paralyze skeletal
muscles)
e) when cations rush in-depolarization of synaptic cell
f) fast, short-acting synaptic potentials
Nicotinic and Muscarinic Acetylcholine
Receptors
Acetylcholine, “Continued”
2) Cholinergic muscarinic receptors (one of five types):
a) found at the NMJs of cardiac and smooth muscle
cells and glands
b) found on the post-gnglionic neurons of sympathetic
nervous system
c) muscarine (a toxin produced by certain mushrooms)
is an agonist ( hence the name)
d) atropine (sarin) is antagonist (its use in
acetylcholinesterase poisoning)-biological weapon
that
inhibits AChE
e) slow, long-acting synaptic potentials
Acetylcholine Receptor Signaling
“Continued”
Adrenergic Receptor Signaling
“Continued”
“Continued”
Ach-Receptor Agonists and Antagonists
Amine Neurotransmitters--derived from
a single amino acid
Catecholamines (CAMs):
Derived from tyrosine-examples are:
Dopamine (DA), Norepinephrine (NE), Epinephrine (E)
Cells that secrete NE are termed adrenergic neurons
Bind to adrenergic receptors which are either alpha (α)
or beta (β) type
Linked to G-proteins and initiate second messenger
cascade
NE in the CNS is related to arousal, dreaming and
regulating mood
DA in CNS neurons is related to emotion, skeletal
muscle tone and movement
Ctecholamine Biosynthetic Pathway
Release of Epinephrine at a Synaptic
Neuron
5-hydroxytryptamine
Turning Synapses Off
Once its job is done, the neurotransmitter must be
removed from synaptic cleft to prepare the synapse for
the arrival of the next action potential:
A) reuptake by synaptic knob of the presynaptic neuron
by active transport-all neurotransmitters use this method
except acetylcholine
B) Ach is rapidly inactivated by acetylcholinesterase
(AChE) enzyme which splits Ach into acetate and to
choline. Choline is actively taken up by presynaptic
neurons and used to make more Ach
C) Catecholamines (NE)-inactivated by monoamine
oxidase (MAO) action after active reuptake in the
presynaptic axon terminal
* MAO inhibitors are used in the treatment of depression
and anxiety