Neurotransmitters

Generality

Neurotransmitters are endogenous chemical messengers, which the cells of the nervous system (the so-called neurons) use to communicate with each other or to stimulate muscle or glandular cells.

Chemical synapses are sites of functional contact between two neurons or between a neuron and another genus of cell.

There are various classes of neurotransmitters: the class of amino acids, the class of monoamines, the class of peptides, the class of "trace" amines, the class of purines, the class of gases, etc.

The most well-known neurotransmitters include: dopamine, acetylcholine, glutamate, GABA and serotonin.

What are neurotransmitters?

Neurotransmitters are chemicals that neurons - the cells of the nervous system - use to communicate with each other, to act on muscle cells or to stimulate a response from glandular cells.

In other words, neurotransmitters are endogenous chemical messengers, which enable interneuronal communication (i.e. between neurons) and communication between neurons and the rest of the body.

The human nervous system uses neurotransmitters to regulate or direct vital mechanisms, such as heartbeat, lung breathing, or digestion.

Furthermore, night sleep, concentration, mood and so on depend on neurotransmitters.

NEUROTRANSMITTERS AND CHEMICAL SYNAPSES

According to a more specialized definition, neurotransmitters are the carriers of information along the system of so-called chemical synapses.

In neurobiology, the term synapse (or synaptic junction) indicates the sites of functional contact between two neurons or between a neuron and another kind of cell (for example, a muscle cell or a glandular cell).

The function of a synapse is to transmit information between the cells involved, to produce a certain response (for example, the contraction of a muscle).

The human nervous system comprises two types of synapses:

• Electric synapses, in which the communication of information depends on a flow of electric currents through the two cells involved, e
• The aforementioned chemical synapses, in which the communication of information depends on a flow of neurotransmitters through the two affected cells.

A classic chemical synapse consists of three fundamental components, placed in series:

• The pre-synaptic terminal of the neuron from which nerve information comes. The neuron in question is also called a pre-synaptic neuron;
• The synaptic space, that is the space of separation between the two protagonist cells of the synapse. It resides outside the cell membranes and has an "area of ​​extension equal to about 20-40 nanometers;
• The post-synaptic membrane of the neuron, muscle cell or glandular cell to which nerve information must reach. Whether it is a neuron, a muscle cell or a glandular cell, the cell unit to which the postsynaptic membrane belongs is called the postsynaptic element.

The chemical synapse that connects a neuron to a muscle cell is also known as the neuromuscular junction or endplate.

DISCOVERY OF NEUROTRANSMITTERS

Figure: chemical synapse

Until the early twentieth century, scientists believed that communication between neurons and between neurons and other cells occurred exclusively through electrical synapses.

The idea that there might be another mode of communication arose when some researchers discovered the so-called synaptic space.

The German pharmacologist Otto Loewi hypothesized that the synaptic space could be used by neurons to release chemical messengers. It was the year 1921.

Through his experiments on the nervous regulation of cardiac activity, Loewi became the protagonist of the discovery of the first known neurotransmitter: acetylcholine.

Site

In pre-synaptic neurons, neurotransmitters reside within small intracellular vesicles.

These intercellular vesicles are comparable to sacs, delimited by a bilayer of phospholipids similar, in several respects, to the phospholipid bilayer of the plasma membrane of a generic healthy eukaryotic cell.

As long as they remain inside the intracellular vesicles, the neurotransmitters are, so to speak, inert and produce no response.

Mechanism of action

Premise: to understand the mechanism of action of neurotransmitters it is good to have in mind the chemical synapses and their composition, described previously.

The neurotransmitters remain confined inside the intracellular vesicles, until a signal of nerve origin capable of stimulating the release of the vesicles from the container neuron arrives.

The release of the vesicles takes place near the pre-synaptic terminal of the container neuron and involves the release of neurotransmitters into the synaptic space.

In the synaptic space, neurotransmitters are free to interact with the post-synaptic membrane of the nerve cell, muscle or glandular, located in the immediate vicinity and forming part of the chemical synapse.

The interaction between neurotransmitters and post-synaptic membrane is possible thanks to the presence, on the latter, of particular proteins, properly called membrane receptors.

The contact between neurotransmitters and membrane receptors transforms the initial nerve signal (the one that stimulated the release of intracellular vesicles) into a very specific cellular response. For example, the cellular response produced by the interaction between neurotransmitters and the post-synaptic membrane of a muscle cell may consist in the contraction of the muscle tissue to which the aforementioned cell belongs.

At the end of this schematic picture of how neurotransmitters work, it is important to report the following last aspect: the specific cellular response mentioned above "indeed depends on the type of neurotransmitter and the type of receptors present on the post-synaptic membrane.

WHAT IS THE POTENTIAL OF ACTION?

In neurobiology, the nerve signal that stimulates the release of intracellular vesicles is called the action potential.

By definition, the action potential is the phenomenon that takes place in a generic neuron and which involves a rapid change in electrical charge between the inside and outside of the cell membrane of the neuron involved.

In light of this, it should not be surprising when, speaking of nerve signals, experts compare them to electrical impulses: a nerve signal is an electrical type event in all respects.

CHARACTERISTICS OF THE CELLULAR RESPONSE

According to the language of neurobiologists, the cellular response induced by neurotransmitters, at the level of the post-synaptic membrane, can be either excitatory or inhibitory.

An excitatory response is a reaction designed to promote the creation of a nerve impulse in the post-synaptic element.

An inhibitory response, on the other hand, is a reaction designed to inhibit the creation of a nerve impulse in the post-synaptic element.

Classification

There are many known human neurotransmitters and their list is bound to grow as neurobiologists regularly discover new ones.

The large number of recognized neurotransmitters has made it essential to classify these chemical molecules, in order to simplify their consultation.

There are various classification criteria; the most common is that which distinguishes neurotransmitters on the basis of the class of molecules they belong to.

The main classes of molecules to which human neurotransmitters belong are:

• The class of amino acids or amino acid derivatives. This class includes: glutamate (or glutamic acid), aspartate (or aspartic acid), gamma-aminobutyric acid (better known as GABA) and glycine.
• The class of peptides. This class includes: somatostatin, opioids, substance P, some secretins (secretin, glucagon, etc.), some tachykinins (neurokinin A, neurokinin B, etc.), some gastrins, galanin, neurotensin and the so-called transcripts regulated by cocaine and amphetamine.
• The class of monoamines. This class includes: dopamine, norepinephrine, epinephrine, histamine, serotonin and melatonin.
• The class of the so-called "trace amines". Included in this class are: tyramine, tri-iodothyronamine, 2-phenylethylamine (or 2-phenylethylamine), octopamine and tryptamine (or tryptamine).
• The class of purines. This class includes: adenosine triphosphate and adenosine.
• The gas class. This class includes: nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S).
• Other. All those neurotransmitters that cannot be included in any of the previous classes, such as the aforementioned acetylcholine or anandamide, fall under the heading “other”.

Best known examples

Some neurotransmitters are much more famous than others, both because they have been known and studied for longer, and because they perform functions of considerable biological interest.

Among the most famous neurotransmitters deserve a mention:

• Glutamate.It is the main excitatory neurotransmitter of the central nervous system: according to what neurobiologists say, more than 90% of the so-called excitatory synapses make use of it.

  Alongside its excitatory function, glutamate is also involved in learning processes (learning understood as a process of storing data in the brain) and memory.
  According to some scientific studies, it would be implicated in diseases such as: Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (better known as ALS) and Parkinson's.

• GABA. It is the main inhibitory neurotransmitters of the central nervous system: according to the latest biology studies, about 90% of the so-called inhibitory synapses would use it.
  Due to its inhibitory properties, GABA is one of the main targets of sedative and tranquilizing drugs.
• Acetylcholine. It is a neurotransmitter with an excitatory function on the muscles: in the neuromuscular junctions, in fact, its presence sets in motion those mechanisms that contract the cells of the muscle tissues involved.
  Besides acting on the muscular level, acetylcholine also influences the functioning of the organs controlled by the so-called autonomic nervous system. Its influence on the autonomic nervous system can be both excitatory and inhibitory.
• Dopamine. Belonging to the catecholamine family, it is a neurotransmitter that performs numerous functions, both at the level of the central nervous system and at the level of the peripheral nervous system.
  At the level of the central nervous system, dopamine participates in: the control of movement, the secretion of the hormone prolactin, the control of motor skills, the reward and pleasure mechanisms, the control of attention skills, the sleep mechanism, the behavior control, the control of certain cognitive functions, the control of mood and, finally, the mechanisms underlying learning.
  At the level of the peripheral nervous system, on the other hand, it acts as: vasodilator, stimulant of sodium excretion, a factor that favors intestinal motility, a factor that reduces lymphocyte activity and, finally, a factor that reduces insulin secretion.
• Serotonin. It is a neurotransmitter present mainly in the intestine and, although to a lesser extent than in the cells of the intestine, in the neurons of the central nervous system.
  From the inhibitory effects, serotonin seems to regulate appetite, sleep, memory and learning processes, body temperature, mood, some aspects of behavior, muscle contraction, some functions of the cardiovascular system and some functions of the endocrine system. .
  From a pathological point of view, it seems to have a role in the development of depression and related diseases. This explains the existence on the market of so-called selective serotonin reuptake inhibitors, antidepressant drugs used for the treatment of more or less severe forms of depression.
• Histamine. It is a neurotransmitter with a prevalent seat in the central nervous system, precisely at the level of the hypothalamus and mast cells present in the brain and spinal cord.
• Norepinephrine and epinephrine. Norepinephrine is concentrated above all in the central nervous system and has the task of mobilizing the brain and body for action (therefore it has an excitatory effect). For example, in the brain, it promotes arousal, alertness, concentration and memory processes; in the rest of the body, it increases heart rate and blood pressure, stimulates the release of glucose from storage points, increases the flow of blood to skeletal muscles, reduces blood flow to the gastrointestinal system and promotes bladder and bowel emptying.
  Epinephrine is present to a large extent in the cells of the adrenal glands and, in small quantities, in the central nervous system.
  This neurotransmitter has excitatory effects and participates in processes such as: the increase of the blood to the skeletal muscles, the increase of the heart rate and the dilation of the pupils.
  Both norepinephrine and epinephrine are neurotransmitters derived from tyrosine.