Neurotransmitters - Classification, Function, Synthesis, Release and Detection Methods

Definition and Classification of Neurotransmitters

Neurotransmitters, a specific group of chemicals that act as messengers in neurosynaptic signaling, have only inhibitory and excitatory effects. Cells in the brain use them to communicate and exchange information with other cells. Without neurotransmitters, our memory, pleasure, desire, ability to learn, etc. would not exist in their present form.

Neurotransmitters in the brain are divided into four categories: biogenic amines, amino acids, peptides, and others.

Biogenic amine: dopamine (DA), norepinephrine (NE), epinephrine (E), 5-hydroxytryptamine (5-HT).

Amino acid: gamma-aminobutyric acid (GABA), glycine, glutamate, histamine, acetylcholine (Ach).

Peptide: endogenous opioid peptide, substance P, neuropressin, cholecystokinin (CCK), growth inhibitor, vasopressin and contractin, neuropeptide y.

Other types of neurotransmitters include: nucleotides, arachidonic acid base, anandamide, and sigma receptors. Nitric oxide is then universally recognized as a neurotransmitter, which is not released in a cytosolic manner, but crosses the cell membrane by virtue of its lipolytic nature, acts and is inactivated by chemical reactions. It acts as a retrograde messenger in synaptic plasticity changes, long time course enhancement effects.

Functions of Common Neurotransmitters

• Amino acids (the most basic neurotransmitters)

Glutamate - representative excitatory neurotransmitter

Gamma-aminobutyric acid - a representative inhibitory neurotransmitter

Glycine - inhibitory neurotransmitter

• Monoamines (substances made up of amino acids)

Acetylcholine - the earliest discovered neurotransmitter, excitatory neurotransmitter, associated with memory, etc.

[Catecholamines]

Dopamine - excitatory neurotransmitter, associated with pleasure and energy

Norepinephrine - excitatory neurotransmitter, related to anger and motivation

Adrenaline - excitatory neurotransmitter, associated with fear and motivation

[Indoleamines]

5-Hydroxytryptamine - neurotransmitter that plays a regulatory role in stabilizing nerves, etc.

Melatonin - related to sleep and other biological clocks

• Neuropeptides (substances composed of more than 2 amino acids)

Aminopolyphenols--reduce pain, bring happiness

Enkephalin--Reduces pain, brings happiness

Where Are Neurotransmitters Synthesized?

• Acetylcholine is synthesized from choline and acetyl coenzyme A catalyzed by choline acetyltransferase. Since this enzyme is present in the cytosol, acetylcholine is synthesized in the cytosol. After synthesis, it is taken up by the vesicles and stored.
• Norepinephrine is synthesized with tyrosine as a raw material. First, dopamine is synthesized in the cytosol, catalyzed by tyrosine hydroxylase, and then dopamine is synthesized by dopa decarboxylase. Dopamine is then taken up into the vesicles, where it is further synthesized by dopamine β-hydroxylase and stored in the vesicles.
• The synthesis of dopamine is identical to the first two steps of norepinephrine, except that norepinephrine is no longer synthesized after dopamine enters the vesicles. This is because the vesicles where dopamine is stored do not contain dopamine β-hydroxylase.
• 5-Hydroxytryptamine is synthesized from tryptophan by the action of tryptophan hydroxylase. Subsequently, 5-hydroxytryptophan is synthesized into 5-hydroxytryptamine by the action of 5-hydroxytryptophan acid decarboxylase (amino acid decarboxylase). This two-step process takes place in the cytosol. Then 5-hydroxytryptophan is taken up into the vesicles and stored in the vesicles.
• Gamma-aminobutyric acid is synthesized by glutamate catalyzed by glutamic acid decarboxylation. The synthesis of peptide transmitters is exactly the same as that of other peptide hormones. It is genetically regulated and synthesized by translation at the ribosome.

Neurotransmitters synthesis, storage in vesicles, transport to presynaptic membrane upon membrane depolarization and Ca²⁺ release, then release of vesicle content into the synapse and re-uptake by specific transporters (SERT, DAT) (van et al., 2021)

How Are Neurotransmitters Released?

When the nerve impulse reaches the terminal, the terminal generates an action potential and ion transfer Ca²⁺ from outside the membrane into the membrane, causing a certain number of vesicles to fuse tightly with the presynaptic membrane. Then a rupture occurs at the point where the vesicles are bonded to the presynaptic membrane. The vesicles then release transmitters and other contents into the synaptic gap. The process of releasing transmitters from the presynaptic membrane is called exocytosis.

Immediately after release from the presynaptic membrane, the neurotransmitter binds to the corresponding postsynaptic membrane receptor, generating a synaptic depolarization potential or hyperpolarization potential, resulting in an increase or decrease in postsynaptic nerve excitability. Since then, the electrical signal of the nerve impulse completes an inter-synaptic crossing.

How Are Neurotransmitters Aborted?

The action of neurotransmitters can be aborted by two pathways.

A. Recycling inhibition. Recycling of excess neurotransmitter from the synaptic gap to the presynaptic neuron and storage in the vesicle via presynaptic carriers.

B. Enzymatic dissociation. In the case of dopamine (DA), it is metabolized and inactivated by the action of monoamine oxidase (MAO) located in the mitochondria and catecholamine neighboring methyltransferase (COMT) located in the cytoplasm.

How Are Neurotransmitters Detected?

Creative Proteomics offers LC-MS/MS technology to analyze neurotransmitters and their derivatives to elucidate their functions in signal transduction processes. Our neurotransmitter analysis platform offers the following advantages.

• High specificity and accuracy: precise characterization and absolute quantification using MRM technology
• Advanced platform: Sciex Q-trap mass spectrometry with wide linear range
• Strict quality control: internal standard + external standard. Manual calibration of standards. Standard R2>0.99

UPLC-MS/MS-based profiling of 31 neurochemicals (Kim et al., 2021)

References

1. van Karnebeek, C. D., et al. (2021). Secondary biogenic amine deficiencies: genetic etiology, therapeutic interventions, and clinical effects. neurogenetics, 22(4), 251-262.
2. Kim, S. S., Lee, H. Y., Song, J. S., Bae, M. A., & Ahn, S. (2021). UPLC-MS/MS-based profiling of 31 neurochemicals in the mouse brain after treatment with the antidepressant nefazodone. Microchemical Journal, 169, 106580.