Neurotransmitters

By: Rana Muhammad Luqman Khan

 Introduction

Neurotransmitters are substances which

neurons use to communicate with one
another and with their target tissues in the
process of synaptic transmission
(neurotransmission).

Neurotransmitters are synthetized in and

released from nerve endings into the
synaptic cleft. From there,
neurotransmitters bind to receptor
proteins in the cellular membrane of the
target tissue. The target tissue gets
excited, inhibited, or functionally modified
in some other way.
 Mechanism of
Neurotransmitters
Neurons communicate with their target tissues at synapses into which they release
chemical substances called neurotransmitters (ligands). As this communication is
mediated with chemical substances, the process is called chemical neurotransmission
and happens within chemical synapses.
Each synapse consists of the:
• Presynaptic membrane – membrane of the terminal bouton (axon ending) of the
presynaptic nerve fiber
• Postsynaptic membrane – membrane of the target cell
• Synaptic cleft – a gap between the presynaptic and postsynaptic membranes
Inside the terminal bouton of the presynaptic nerve fiber, numerous vesicles that contain
neurotransmitters are produced and stored. When the presynaptic membrane is
depolarized by an action potential, calcium voltage-gated channels open (found in the
membranes of the terminal buttons). This leads to an influx of calcium ions into the
terminal bouton, which changes the state of certain membrane proteins in the
presynaptic membrane, and results in exocytosis of neurotransmitters from the terminal
bouton into the synaptic cleft.
After crossing the synaptic cleft, neurotransmitters bind to their receptors on the
postsynaptic membrane. Once the neurotransmitter binds to its receptor, the ligand-
gated channels of the postsynaptic membrane either open or close. These ligand-gated
channels are ion channels, and their opening or closing alters the permeability of the
postsynaptic membrane to calcium, sodium, potassium, and chloride ions. This leads to
a stimulatory or inhibitory response.

If a neurotransmitter stimulates the target cell to an action, then it is an excitatory

neurotransmitter acting in an excitatory synapse. On the other hand, if it inhibits the
target cell, it is an inhibitory neurotransmitter acting in an inhibitory synapse. So, the
type of the synapse and the response of the target tissue depends on the type of
neurotransmitter. Excitatory neurotransmitters cause depolarization of the postsynaptic
cells and generate an action potential; for example acetylcholine stimulates muscle
contraction. Inhibitory synapses cause hyperpolarization of the target cells, leading
them farther from the action potential threshold, thus inhibiting their action; for example
GABA inhibits involuntary movements.
Repeated synaptic activities can have long-lasting effects on the receptor neuron,
including structural changes such as the formation of new synapses, alterations in the
dendritic tree, or growth of axons. An example of this is the learning process – the more
you study and repeat, the more synapses are created in your brain and enable you to
retrieve that information when needed.
Mechanism of Neurotransmitters
Seven Steps
 Classification

Neurotransmitters can be classified as either excitatory or inhibitory. Excitatory

neurotransmitters function to activate receptors on the postsynaptic membrane and
enhance the effects of the action potential, while inhibitory neurotransmitters function to
prevent an action potential. In addition to the above classification, neurotransmitters can
also be classified based on their chemical structure:

• Amino acids – GABA, glutamate

• Monoamines – serotonin, histamine
• Catecholamines (subcategory of monoamines) – dopamine, norepinephrine,
epinephrine
Types of Neurotransmitters
Excitatory & Inhibitory
 Acetylcholine (ACh)

Acetylcholine (ACh) is an excitatory neurotransmitter secreted by motor neurons that

innervate muscle cells, basal ganglia, preganglionic neurons of the autonomic nervous
system, and postganglionic neurons of the parasympathetic and sympathetic nervous
systems.

Its main function is to stimulate muscle contraction. However, the only exception to this,
where acetylcholine is an inhibitory neurotransmitter, is at the parasympathetic endings
of the vagus nerve. These inhibit the heart muscle through the cardiac plexus.

It is also found in sensory neurons and in the autonomic nervous system, and has a part
in scheduling the “dream state” while an individual is fast asleep. Acetylcholine plays a
vital role in the normal functioning of muscles.
 Norepinephrine (NE)
Norepinephrine (NE), also known as noradrenaline (NAd), is an excitatory
neurotransmitter produced by the brainstem, hypothalamus, and adrenal glands and
released into the bloodstream.The adrenal medulla produces norepinephrine in response
to low blood pressure and stress. Norepinephrine promotes vasoconstriction, which is a
narrowing of the blood vessels, and this increases blood pressure.
Like epinephrine, norepinephrine also increases the heart rate and blood sugar levels.

In the body, it is secreted by most postganglionic sympathetic nerves. It acts to stimulate

the processes in the body. For example, it is very important in the endogenous
production of epinephrine.

Norepinephrine has been implicated in mood disorders such as depression and

anxiety, in which case its concentration in the body is abnormally low. Alternatively, an
abnormally high concentration of it may lead to an impaired sleep cycle.
 Epinephrine (EPI)

Also known as adrenaline (Ad), epinephrine (Epi) is an excitatory neurotransmitter

produced by the chromaffin cells of the adrenal gland. It prepares the body for the fight-
or-flight response. That means that when a person is highly stimulated (fear, anger etc.),
extra amounts of epinephrine are released into the bloodstream.

This release of epinephrine increases heart rate, blood pressure, and glucose release
from the liver (via glycogenolysis). In this way, the nervous and endocrine systems
prepare the body for dangerous and extreme situations by increasing nutrient supply to
key tissues.
 Dopamine (DA)
Dopamine (DA) is a neurotransmitter secreted by the neurons of the substantia nigra. It
is considered a special type of neurotransmitter because its effects are both excitatory
and inhibitory. Which effect depends on the type of receptor that dopamine binds to.

As a part of the extrapyramidal motor system which involves the basal ganglia,
dopamine is important for movement coordination by inhibiting unnecessary movements.
In the pituitary gland, it inhibits the release of prolactin, and stimulates the secretion of
growth hormone.

Dopamine deficiency related to the destruction of the substantia nigra leads to

Parkinson’s disease. Increased activity of dopaminergic neurons contributes to the
pathophysiology of psychotic disorders and schizophrenia. Drug and alcohol abuse can
temporarily increase dopamine levels in the blood, leading to confusion and the inability
to focus. However, an appropriate secretion of dopamine in the bloodstream plays a role
in the motivation or desire to complete a task
 Gamma-Aminobutyric Acid
(GABA)

Gamma-Aminobutyric acid (GABA) is the most powerful inhibitory neurotransmitter

produced by the neurons of the spinal cord, cerebellum, basal ganglia, and many areas
of the cerebral cortex. It is derived from glutamate.

Functions of GABA are closely related to mood and emotions. It is an inhibitory

neurotransmitter that acts as a brake to excitatory neurotransmitters; thus when it is
abnormally low this can lead to anxiety. It is widely distributed in the brain and plays a
principal role in reducing neuronal excitability throughout the nervous system.
 Glutamate (Glu)

Glutamate (Glu) is the most powerful excitatory neurotransmitter of the central

nervous system which ensures homeostasis with the effects of GABA. It is secreted by
neurons of the many of the sensory pathways entering the central nervous system, as
well as the cerebral cortex.

Glutamate is the most common neurotransmitter in the central nervous system; it takes
part in the regulation of general excitability of the central nervous system, learning
processes, and memory. Thus, inappropriate glutamate neurotransmission contributes to
developing epilepsy and cognitive and affective disorders.
 Serotonin

Serotonin (5-hydroxytryptamine, 5-HT) is an inhibitory neurotransmitter that has been

found to be intimately involved in emotion and mood. It is secreted by the neurons of the
brainstem and by neurons that innervate the gastrointestinal tract (enteric nervous
system). In addition, serotonin is found in platelets (thrombocytes) which release it during
coagulation (hemostasis).

It participates in regulation of body temperature, perception of pain, emotions, and sleep

cycle. An insufficient secretion of serotonin may result in decreased immune system
function, as well as a range of emotional disorders like depression, anger control
problems, obsessive-compulsive disorder, and even suicidal tendencies.
 Histamine

Histamine is an excitatory neurotransmitter produced by neurons of the hypothalamus,

cells of the stomach mucosa, mast cells, and basophils in the blood. In the central
nervous system, it is important for wakefulness, blood pressure, pain, and sexual
behavior. In the stomach, it increases the acidity.

It is involved primarily in the inflammatory response, as well as a range of other

functions such as vasodilation and regulation of the immune response to foreign bodies.
For example, when allergens are introduced into the bloodstream, histamine assists in
the fight against these microorganisms causing itching of the skin or irritations of the
throat, nose, and or lungs.