Neurotransmitters: Definition, Mechanism, Identification, Types, Effects of Drugs, Associated Diseases and Disorders

They are endogenous chemicals that allow neurotransmission.

It is a type of chemical messenger that transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another “target” neuron, muscle cell, or gland.

Neurotransmitters are released from synaptic vesicles at synapses to the synaptic cleft, where neurotransmitter receptors receive them on target cells.

Many neurotransmitters are synthesized from simple and abundant precursors, such as amino acids, that are readily available in the diet and require only a small number of biosynthetic steps for conversion.

Neurotransmitters play an important role in shaping everyday life and functions. Their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified.

Mechanism

Neurotransmitters are stored at a synapse in synaptic vesicles, clustered below the membrane at the axon terminal located on the presynaptic side of the synapse.

Neurotransmitters are released and diffuse across the synaptic cleft, where they bind to specific receptors on the membrane on the postsynaptic side of the synapse.

Most neurotransmitters are about the size of a single amino acid, however some neurotransmitters can be the size of larger proteins or peptides.

Generally, a released neurotransmitter is available in the synaptic cleft for a short period of time before being metabolized by enzymes, retracting to the presynaptic neuron through reuptake, or binding to a postsynaptic receptor.

However, short-term exposure of the receptor to a neurotransmitter is usually sufficient to elicit a postsynaptic response through synaptic transmission.

In response to a threshold action potential or gradual electrical potential, a neurotransmitter is released at the presynaptic terminal.

Low-level “low” release also occurs without electrical stimulation. The released neurotransmitter can move across the synapse to be detected by and bind to receptors on the postsynaptic neuron.

Neurotransmitter binding can influence the postsynaptic neuron in an inhibitory or excitatory way. This neuron can be connected to many more neurons, and if the total of excitatory influences is greater than the inhibitory influences, the neuron will also “fire.”

Ultimately, it will create a new action potential in your hillock axon to release neurotransmitters and transmit the information to another neighboring neuron.

ID

There are four main criteria for identifying neurotransmitters:

  • The chemical must be synthesized in the neuron or be present in it.
  • When the neuron is active, the chemical must be released and produce a response on some target.
  • The same response should be obtained when the chemical is experimentally placed on the target.
  • There must be a mechanism in place to remove the chemical from its activation site after its work.

However, given advances in pharmacology, genetics, and chemical neuroanatomy, the term “neurotransmitter” can be applied to chemicals that:

  • Transmit messages between neurons through influence on the postsynaptic membrane.
  • They have little or no effect on membrane voltage, but have a common transport function, such as changing the structure of the synapse.
  • Communicate by sending reverse direction messages that affect the release or recapture of transmitters.

The anatomical location of neurotransmitters is typically determined by immunocytochemical techniques, which identify the location of the transmitting substances themselves or of the enzymes involved in their synthesis.

Immunocytochemical techniques have also revealed that many transmitters, particularly neuropeptides, are co-localized, that is, a neuron can release more than one transmitter from its synaptic terminal.

Various techniques and experiments such as staining, stimulation, and harvesting can be used to identify neurotransmitters throughout the central nervous system.

Types

There are many different ways to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.

Main neurotransmitters:

  • Amino acids: glutamate, aspartate, D-serine, γ-aminobutyric acid (GABA), glycine.
  • Gas transmitters: nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H 2 S).
  • Monoamines: dopamine (DA), norepinephrine (norepinephrine, NE, NA), epinephrine (adrenaline), histamine, serotonin (SER, 5-HT).
  • Raster amines: phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronine, octopamine, tryptamine, etc.
  • Peptides: somatostatin, substance P, regulated transcription of cocaine and amphetamine, opioid peptides.
  • Purines: adenosine triphosphate (ATP), adenosine.
  • Others: acetylcholine (ACh), anandamide, etc.

In addition, more than 50 neuroactive peptides have been found and new ones are discovered regularly. Many of these are “co-launched” together with a small molecule transmitter.

However, in some cases, a peptide is the primary transmitter at a synapse.

Beta-endorphin is a relatively well-known example of a peptide neurotransmitter because it deals with highly specific interactions with opioid receptors in the central nervous system.

The most common transmitter is glutamate, which is excitatory in more than 90% of synapses in the human brain.

The next most prevalent is Gamma-Aminobutyric Acid, or GABA, which is inhibitory in over 90% of non-glutamate synapses.

Although other transmitters are used in a few synapses, they can be very important from a functional point of view: the vast majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or the GABA.

Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system.

Addictive opioid drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine levels.

Actions

Neurons form elaborate networks through which nerve impulses (action potentials) travel. Each neuron has up to 15,000 connections to neighboring neurons.

Neurons don’t touch each other; Instead, neurons interact at points of contact called synapses: a junction within two nerve cells, consisting of a miniature space within which impulses are carried by a neurotransmitter.

A neuron carries its information through a nerve impulse called an action potential.

When an action potential reaches the presynaptic terminal button of the synapse, it can stimulate the release of neurotransmitters.

These neurotransmitters are released in the synaptic cleft to bind to receptors on the postsynaptic membrane and influence another cell, either in an inhibitory or an excitatory way.

The next neuron may be connected to many more neurons, and if the total of excitatory influences minus inhibitory influences is large enough, it will be too. ‘

Drug effects

Understanding the effects of drugs on neurotransmitters comprises an important part of research initiatives in the field of neuroscience.

Most neuroscientists involved in this field of research believe that such efforts can advance our understanding of the circuits responsible for various neurological diseases and disorders, as well as ways to effectively treat and possibly prevent or cure such diseases one day.

Drugs can influence behavior by altering the activity of neurotransmitters.

For example, drugs can decrease the rate of neurotransmitter synthesis by affecting the synthetic enzyme (s) for that neurotransmitter.

When neurotransmitter syntheses are blocked, the amount of neurotransmitters available for release becomes substantially lower, resulting in a decrease in neurotransmitter activity.

Some drugs block or stimulate the release of specific neurotransmitters. Alternatively, drugs can prevent the storage of neurotransmitters in synaptic vesicles by causing the membranes of the synaptic vesicles to leak.

Drugs that stop a neurotransmitter from binding to its receptor are called receptor antagonists. For example, medications used to treat patients with schizophrenia such as haloperidol, chlorpromazine, and clozapine are antagonists of dopamine receptors in the brain.

Other drugs work by binding to a receptor and mimicking the normal neurotransmitter. These drugs are called receptor agonists.

An example of a receptor agonist is morphine, an opiate that mimics the effects of the endogenous neurotransmitter β-endorphin to relieve pain.

Other drugs interfere with the deactivation of a neurotransmitter after it has been released, thereby prolonging the action of a neurotransmitter. This can be achieved by blocking reuptake or by inhibiting degradative enzymes.

Lastly, medications can also prevent an action potential from occurring, blocking neural activity throughout the central and peripheral nervous system. Medications such as tetrodotoxin that block neuronal activity are generally lethal.

Drugs targeting the neurotransmitter of the major systems affect the entire system, which may explain the complexity of the action of some drugs.

Cocaine, for example, blocks dopamine reuptake in the presynaptic neuron, leaving neurotransmitter molecules in the synaptic gap for an extended period of time.

Since dopamine remains in the synapse longer, the neurotransmitter continues to bind to receptors on the postsynaptic neuron, causing a pleasant emotional response.

Physical addiction to cocaine can be the result of prolonged exposure to excess dopamine at synapses, leading to down-regulation of some postsynaptic receptors.

After the effects of the drug wear off, an individual may become depressed due to a lower likelihood that the neurotransmitter will bind to a receptor.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), which blocks the reuptake of serotonin by the presynaptic cell, thereby increasing the amount of serotonin present in the synapse and also allowing it to remain there longer, providing potential for the released effect of serotonin.

Diseases and disorders

Diseases and disorders can also affect specific neurotransmitter systems.

For example, problems in dopamine production can lead to Parkinson’s disease, a disorder that affects a person’s ability to move as they want, leading to stiffness, tremors or tremors, and other symptoms.

Some studies suggest that having too little or too much dopamine or problems using dopamine in the thinking and feeling regions of the brain may play a role in disorders such as schizophrenia or attention deficit hyperactivity disorder (ADHD).

Similarly, after some research suggested that drugs that block the recycling, or reuptake, of serotonin seemed to help some people diagnosed with depression, it was theorized that people with depression might have lower-than-normal serotonin levels. .

Although widely popularized, this theory was not confirmed in later research.

Additionally, problems with glutamate production or use have been suggestive and tentatively linked to many mental disorders, including autism, obsessive compulsive disorder (OCD), schizophrenia, and depression.

Neurotransmitter imbalance

In general, there are no scientifically established “norms” for appropriate levels or “balances” of different neurotransmitters.

In most cases, it is virtually impossible to measure neurotransmitter levels in the brain or body at any point in time.

Neurotransmitters regulate the release of each other, and the weak imbalances consistent in this mutual regulation were related to temperament in healthy people.

Strong imbalances or disruptions in neurotransmitter systems have been associated with many mental illnesses and disorders.

These include Parkinson’s, depression , insomnia, attention deficit hyperactivity disorder (ADHD), anxiety, memory loss, drastic changes in weight, and addictions.

Chronic physical or emotional stress can contribute to changes in the neurotransmitter system. Genetics also play a role in neurotransmitter activities.

In addition to recreational use, medications that interact directly and indirectly with one or more transmitters or receptors are commonly prescribed for psychiatric and psychological problems.

In particular, drugs that interact with serotonin and norepinephrine are prescribed to patients with problems such as depression and anxiety, although the idea that there is a lot of solid medical evidence to support such interventions has been widely criticized.

Neurotransmitter removal

A neurotransmitter must be broken down once it reaches the postsynaptic cell to prevent further excitatory or inhibitory signal transduction.

This allows new signals to be produced from adjacent nerve cells. When the neurotransmitter has been secreted into the synaptic cleft, it binds to specific receptors on the postsynaptic cell, thus generating a postsynaptic electrical signal.

The transmitter must be removed quickly to allow the postsynaptic cell to participate in another cycle of neurotransmitter release, binding, and signal generation.

Neurotransmitters are terminated in three different ways:

  • Diffusion: the neurotransmitter separates from the receptor, leaving the synaptic cleft, here it becomes absorbed by glial cells.
  • Enzyme breakdown – Special chemicals called enzymes break it down.
  • Repetition: reabsorption of a neurotransmitter in the neuron. Transporters, or membrane transporter proteins, pump neurotransmitters from the synaptic cleft to the axon terminals (the presynaptic neuron) where they are stored.

For example, choline takes up and recycles choline through the presynaptic neuron to synthesize more ACh.

Other neurotransmitters such as dopamine are able to diffuse away from their targeted synaptic junctions and are either removed from the body through the kidneys or destroyed in the liver.

Each neurotransmitter has very specific degradation pathways at regulatory points, which can be attacked by the body’s regulatory system or by recreational drugs.