Noradrenergic Transmission

To start off I think it is important to explain what exactly the noradrenergic transmission is. The
noradrenergic transmission is a neuronal system which releases a neurotransmitter called
noradrenaline, which is a chemical substance that transmits a nerve impulse; and this impulse
causes a body to react in a situation. This reaction, in psychology, is known as the “fight or flight”
reaction which can be caused for numerous reasons. This explanation is completely basic but as I go
on I will describe the noradrenergic transmission and how it is interfered with in further detail; but
first I will have to start off explaining what the autonomic nervous system (ANS) is as it directly
connected with the noradrenergic system.

The noradrenergic transmission is part of the sympathetic nervous system (SNS) which is one half of
the autonomic nervous system (ANS), which is part of the peripheral nervous system (PNS) which
connects to the central nervous system (CNS). The autonomic nervous system is an efferent system,
this means it transmits impulses from the central nervous system to an ‘effector,’ which can be a
visceral organ, which carries out a response to this impulse. This means an impulse from the
sympathetic nervous system involving the noradrenergic transmission can provide regulations of the
smooth muscles, cardiac muscles, and glandular secretions. Which means it can even control the
heart rate by means of contracting and relaxing the muscles in the heart through motor nerve fibres.
The autonomic nervous system is, however, involuntary; meaning it has a subconscious control over
it’s impulses. An example to understand that is breathing while sleeping. You do it subconsciously
and it’s caused by the impulses sent to the central nervous system from the ANS. The autonomic
nerves make changes necessary to guarantee optimal support for the body’s activities. The
connection the autonomic system has with the noradrenergic transmission is that it releases
noradrenalin, or also known as norepinephrine (NE) which is the neurotransmitter that triggers the
‘fight or flight’ response.

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 To clearly understand this is by looking at
Figure 1 which I carefully picked. Starting
from the left hand side of the diagram and
following the Autonomic nervous system to
the sympathetic division, which in the body
is found in the spinal cord. You can see the
central nervous system has a motor neuron
that’s not labelled in the diagram but is
known as the preganglionic neuron. The
axon of it, the preganglionic axon, synapses
Figure 1. with the second motor neuron known as the
autonomic ganglion, labelled just “ganglion”
in Figure 1. It’s axon known as

the post ganglionic axon, and it extends to an effector organ releasing norepinephrine and thus
causing the ‘fight or flight’ reaction.

So it is through sympathetic nervous system which is within the ANS that norepinephrine is actually
released. And as stated before, it would happen involuntarily. Norepinephrine is a monoamine and is
synthesised from an amino acid called tyrosine. As you can see from Figure 2 the tyrosine starts off
in the adrenal medulla and converts tyrosine into
dihydroxyphenylalanine by adding a hydroxyl group to
it. Then that is decarboxylated to dopamine. After that
the dopamine is hydroxylated in the β-position to
norepinephrine. The enzymes involved for each step
are labelled in figure 2.

However if the Dopamine is α-methyl type then a α-

position norepinephrine is produced and this has
therapeutic implications. α and β both have agonist
sensitivities as the α receptors are stimulated at lower
concentrations by norepinephrine than β receptors
are.

Figure 2. Norepinephrine once made is packaged in

vesicles. Most of the norepinephrine is moved into synaptic vesicles with ATP and some other
proteins and then is moved to nerve terminals, where it is stored. The nerve terminal can be
activated by an influx of calcium ions. This initiates exocytosis by inducing depolarisation; the
vesicles are released slowly into the synaptic cleft by adrenergic synapses. Once released
norepinephrine binds to specific receptors, and will contain information for either inhibitory or
excitatory effects for a specific visceral organs in the body, and so can be supplied throughout the
CNS. Secretion of Norepinephrine can be terminated by a reuptake mechanism in the presynaptic
membrane, which is part of the cell membrane of an axon terminal that establishes a synapse. This

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 uptake is called uptake-1 and is energy dependant. There’s also uptake-2 which is less avid, however,
it is concentrated by a vesicle and can be reused by the nerve in future situations.

As discussed before there are both α-position and β-position norepinephrine receptors. They can
even be further classed into the subtypes α1 and α2; and into β1, β2 and β3 subtypes. The α2 can be
found in adrenergic neurones, in the smooth muscle, blood vessels and even the pancreas however
if coupled by G-proteins, the α2 receptors can have an inhibitory effect on neurotransmission when
bound by an agonist; but if bound by an antagonist like doxazosin, which is an α blocker, then the
effect can be reversed and the α2 receptor will not affect neurotransmission.

There are also other drugs that can affect the noradrenergic transmission. Drugs can target specific
inhibitory or stimulatory effects on targeted organs. An example is Reserpine; this can interfere with
synaptic vesicle uptake meaning it can block noradrenalin uptake. It is an anti-hypertensive drug but
because noradrenaline, the “feel good” drug as it is known, can’t be transmitted then this could lead
to depression. There are also drugs that interfere with the pre-synaptic re-uptake of noradrenaline;
an example being desipramine. This allows for more noradrenaline to be in the system and thus why
it’s called an anti-depressant. Cocaine acts in a similar way giving increased sympathetic outflow
meaning more noradrenaline.

In conclusion the noradrenergic transmission is activated by a series of systems to regulate the body
in times of need, by releasing a neurotransmitter called noradrenaline. The “fight or flight” reaction
Figure 2
is a response to when something sudden happens and the body ‘reflexes’ that by releasing
noradrenaline to allow itself to be ‘calm’. Drugs can increase or decrease the secretion of
noradrenaline to either be used as a anti-depressant or prevent hyper-tension.

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Bibliography:

Diagrams:

Figure 1 taken from http://faculty.irsc.edu/FACULTY/TFischer/AP1/somatic%20vs%20autonomic.jpg

Figure 2 taken from http://ardb.bjmu.edu.cn/image/ligand01.jpg

Books:

Elaine N. Marieb and Katja Hoehn, Human anatomy and physiology, 8th edition, Pearson.

S. Marc Breedlove, Mark R. Rosenweig and Neil V. Watson, Biological psychology, 5th edition,
Sinauer.

Sci-Tech Encyclopedia, McGraw-Hill Encyclopedia of Science and Technology, 5th edition, The
McGraw-Hill Companies, Inc.

A.R Crossman and D, Neary, Neuroanatomy, 3rd edition, Churchill livingstone.

Martini Bartholomew, Anatomy and physiology, 7th edition published by pearson.

Andrew Davies, Asa G.H. Blakeley and Cecil Kidd, Human physiology, Churchill livingstone.

Websites:

http://www.cnsforum.com/imagebank/section/receptor_systems_Noradrenergic/default.aspx

http://www.nda.ox.ac.uk/wfsa/html/u05/u05_010.htm

http://www.anaesthetist.com/anaes/patient/ans/Findex.htm#nadr.htm

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