What are neurotransmitters?

Neurotransmitter is a chemical substance which is released at the end of a nerve fibre by the arrival of a nerve impulse and, by diffusing across the synapse or junction, effects the transfer of the impulse to another nerve fibre, a muscle fibre, or some other structure.

Discovery of Neurotransmitters

In 1921, an Austrian scientist named Otto Loewi discovered the first neurotransmitter. In his experiment (which came to him in a dream), he used two frog hearts.

One heart (heart #1) was still connected to the vagus nerve. Heart #1 was placed in a chamber that was filled with saline. This chamber was connected to a second chamber that contained heart #2. So, fluid from chamber #1 was allowed to flow into chamber#2.

Electrical stimulation of the vagus nerve (which was attached to heart #1) caused heart #1 to slow down. Loewi also observed that after a delay, heart #2 also slowed down. From this experiment, Loewi hypothesized that electrical stimulation of the vagus nerve released a chemical into the fluid of chamber #1 that flowed into chamber #2. He called this chemical “Vagusstoff“. We now know this chemical as the neurotransmitter called “acetylcholine“.

Neurotransmitters are often referred to as the body’s chemical messengers. They are the molecules used by the nervous system to transmit messages between neurons, or from neurons to muscles.

Communication between two neurons happens in the synaptic cleft (the small gap between the synapses of neurons). Here, electrical signals that have travelled along the axon are briefly converted into chemical ones through the release of neurotransmitters, causing a specific response in the receiving neuron.

A neurotransmitter influences a neuron in one of three ways: excitatory, inhibitory or modulatory.

An excitatory transmitter promotes the generation of an electrical signal called an action potential in the receiving neuron, while an inhibitory transmitter prevents it. Whether a neurotransmitter is excitatory or inhibitory depends on the receptor it binds to.

Neuromodulators are a bit different, as they are not restricted to the synaptic cleft between two neurons, and so can affect large numbers of neurons at once. Neuromodulators therefore regulate populations of neurons, while also operating over a slower time course than excitatory and inhibitory transmitters.

Most neurotransmitters are either small amine molecules, amino acids, or neuropeptides. There are about a dozen known small-molecule neurotransmitters and more than 100 different neuropeptides, and neuroscientists are still discovering more about these chemical messengers. These chemicals and their interactions are involved in countless functions of the nervous system as well as controlling bodily functions.

Key neurotransmitters

Neurotransmitter Types

There are many types of chemicals that act as neurotransmitter substances. Below is a list of some of them.

1. Small Molecule Neurotransmitter Substances

• Acetylcholine (ACh)
• Dopamine (DA)
• Norepinephrine (NE)
• Serotonin (5-HT)
• Histamine
• Epinephrine

2.Amino Acids

• Gamma-aminobutyric acid (GABA)
• Aspartate
• Glycine
• Glutamate

 

3. Neuroactive Peptides – partial list

• Bradykinin
• beta-endorphin
• bombesin
• calcitonin
• cholecystokinin
• enkephalin
• dynorphin
• insulin
• gastrin
• substance P
• neurotensin
• glucagon
• secretin
• somatostatin
• motilin
• vasopressin
• oxytocin
• prolactin
• thyrotropin
• angiotensin II
• sleep peptides
• galanin
• neuropeptide Y
• thyrotropin-releasing hormone
• gonadotropnin-releasing hormone
• growth hormone-releasing hormone
• luteinizing hormone
• vasoactive intestinal peptide

4. Soluble Gases:

• Nitric Oxide (NO)
• Carbon Monoxide

 

The first neurotransmitter to be discovered was a small molecule called acetylcholine. It plays a major role in the peripheral nervous system, where it is released by motor neurons and neurons of the autonomic nervous system. It also plays an important role in the central nervous system in maintaining cognitive function. Damage to the cholinergic neurons of the CNS is associated with Alzheimer disease.

Glutamate is the primary excitatory transmitter in the central nervous system. Conversely, a major inhibitory transmitter is its derivative γ-aminobutyric acid (GABA), while another inhibitory neurotransmitter is the amino acid called glycine, which is mainly found in the spinal cord.

Many neuromodulators, such as dopamine, are monoamines. There are several dopamine pathways in the brain, and this neurotransmitter is involved in many functions, including motor control, reward and reinforcement, and motivation.

Noradrenaline (or norepinephrine) is another monoamine, and is the primary neurotransmitter in the sympathetic nervous system where it works on the activity of various organs in the body to control blood pressure, heart rate, liver function and many other functions.

Neurons that use serotonin (another monoamine) project to various parts of the nervous system. As a result, serotonin is involved in functions such as sleep, memory, appetite, mood and others. It is also produced in the gastrointestinal tract in response to food.

Histamine, the last of the major monoamines, plays a role in metabolism, temperature control, regulating various hormones, and controlling the sleep-wake cycle, amongst other functions.

Synthesis of Neurotransmitters

Acetylcholine is found in both the central and peripheral nervous systems. Choline is taken up by the neuron. When the enzyme called choline acetyltransferase is present, choline combines with acetyl coenzyme A (CoA) to produce acetylcholine.

Dopamine, norepinephrine and epinephrine are a group of neurotransmitters called “catecholamines”. Norepinephrine is also called “noradrenalin” and epinephrine is also called “adrenalin”. Each of these neurotransmitters is produced in a step-by-step fashion by a different enzyme.

Transport and Release of Neurotransmitters:

Neurotransmitters are made in the cell body of the neuron and then transported down the axon to the axon terminal. Molecules of neurotransmitters are stored in small “packages” called vesicles (see the picture on the right). Neurotransmitters are released from the axon terminal when their vesicles “fuse” with the membrane of the axon terminal, spilling the neurotransmitter into the synaptic cleft.

Unlike other neurotransmitters, nitric oxide (NO) is not stored in synaptic vesicles. Rather, NO is released soon after it is produced and diffuses out of the neuron. NO then enters another cell where it activates enzymes for the production of “second messengers”.

Receptor Binding

Neurotransmitters will bind only to specific receptors on the post-synaptic membrane that recognize them.

Inactivation of Neurotransmitters

The action of neurotransmitters can be stopped by four different mechanisms:
1. Diffusion: the neurotransmitter drifts away, out of the synaptic cleft where it can no longer act on a receptor.

2. Enzymatic degradation (deactivation): a specific enzyme changes the structure of the neurotransmitter so it is not recognized by the receptor. For example, acetyl-cholinesterase is the enzyme that breaks acetylcholine into choline and acetate.

3. Glial cells: astrocytes remove neurotransmitters from the synaptic cleft.

4. Re-uptake: the whole neurotransmitter molecule is taken back into the axon terminal that released it. This is a common way the action of norepinephrine, dopamine and serotonin is stopped…these neurotransmitters are removed from the synaptic cleft so they cannot bind to receptors.
 https://www.biochemden.com/neurotransmitters-neuropepptides/
https://qbi.uq.edu.au/brain/brain-physiology/what-are-neurotransmitters