Neurotransmitters are endogenous chemicals that allow neurons to communicate with each other throughout the body. They enable the brain to provide a variety of functions, through the process of chemical synaptic transmission. These endogenous chemicals are integral in shaping everyday life and functions.[rx]
Neurotransmitter, also called chemical transmitter or chemical messenger, any of a group of chemical agents released by neurons (nerve cells) to stimulate neighboring neurons or muscle or gland cells, thus allowing impulses to be passed from one cell to the next throughout the nervous system.
Chemical synaptic transmission primarily through the release of neurotransmitters from presynaptic neural cells to postsynaptic receptors. Alterations in the levels of specific neurotransmitters have been observed in various neurological disorders, including Parkinson’s disease, schizophrenia, depression, and Alzheimer’s disease.
Types of Neurotransmitters
There are many different ways to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.[rx]
Major neurotransmitters:
- Amino acids – glutamate, aspartate, D-serine, gamma-Aminobutyric acid (GABA), glycine
- Gasotransmitters – nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S)
- Monoamines – dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SER, 5-HT)
- Trace amines – phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronine, octopamine, tryptamine, etc.
- Peptides – oxytocin, somatostatin, substance P, cocaine and amphetamine-regulated transcript, opioid peptides
- Purines – adenosine triphosphate (ATP), adenosine
- Catecholamines – dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline)
- Others: acetylcholine (ACh), anandamide, etc.
In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are co-released along with a small-molecule transmitter. Nevertheless, 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 engages in highly specific interactions with opioid receptors in the central nervous system.
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There are more than 40 neurotransmitters in the human nervous system; some of the most important are acetylcholine, norepinephrine, dopamine, gamma-aminobutyric acid (GABA), glutamate, serotonin, and histamine.
| Excitatory neurotransmitters | Glutamate (Glu) Acetylcholine (ACh) Histamine Dopamine (DA) Norepinephrine (NE); also known as noradrenaline (NAd) Epinephrine (Epi); also known as adrenaline (Ad) |
| Inhibitory neurotransmitters | gamma-Aminobutyric acid (GABA) Serotonin (5-HT) Dopamine (DA) |
| Neuromodulators | Dopamine (DA) Serotonin (5-HT) Acetylcholine (ACh) Histamine Norepinephrine (NE) |
| Neurohormones | Releasing hormones from hypothalamus Oxytocin (Oxt) Vasopressin; also known as antidiuretic hormone (ADH) |
Mechanism
Neurotransmission medication occurs via the vesicular release of neurotransmitters at presynaptic nerve terminals. Specifically, calcium-evoked exocytosis of the presynaptic vesicles is what enables the release of neurotransmitters into the synapse. Active zones, specialized areas on the presynaptic plasma membranes, tether the neurotransmitter-containing vesicles to the plasma membrane. Once an action potential triggers calcium influx into the presynaptic cleft, active zones undergo fusion with the vesicles, allowing neurotransmitter release.[rx] There are multiple proteins involved in the fusion of neurotransmitter-containing vesicles and the active zone. The soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs) syntaxin-1, SNAP-25, and synaptobrevin-2 together form a SNARE complex, a key component in membrane fusion and ultimately exocytosis. A number of the proteins involved in this process may act as inhibitors and activators of the exocytosis of neurotransmitters from the presynapse.[rx]
Development
Neurotransmitters are involved in the processes of early human development, including neurotransmission, differentiation, the growth of neurons, and the development of neural circuitry. Certain neurotransmitters may appear at different points of development. For example, monoamines are present before the neurons are differentiated. Norepinephrine levels are high in the notochord, even in the very early stages of the embryo. Serotonin has a role in morphogenesis. Excitatory amino acids tend to appear later in ontogenesis. The levels of neurotransmitters and neuromodulators tend to increase as new synapses form. Others will appear in the perinatal period, like glutamate, and plateau afterward. Hypoxia and drug-exposure can disturb the formation of neuronal circuity, leading to long-term deleterious effects in the body.[rx][rx]
Function
There are a number of neurotransmitters used by the body for different functions, including acetylcholine, glutamate, GABA, glycine, dopamine, norepinephrine, and serotonin. Glutamate is the principal excitatory neurotransmitter used in the brain. It is also the primary mediator of nervous system plasticity.[rx] Glutamate has been implicated in modifiable synapses, which researchers suspect are the memory-storage elements of the brain.[rx] Gamma-aminobutyric acid (GABA) and glycine, conversely, serve as the major inhibitory neurotransmitters. GABA, for example, can account for approximately 40% of the inhibitory processing in the brain. Glycine is found primarily in the spinal cord.[rx] Dopamine, another major neurotransmitter, plays an essential role in several brain functions, including learning, motor control, reward, emotion, and executive functions. Dopamine has also been implicated in psychiatric and neurological disorders.[7] Serotonin is a neurotransmitter that modulates multiple neuropsychological processes and neural activity — many drugs used in psychiatry and neurology target serotonin. Serotonin also has implications that affect gastrointestinal processes like bowel motility, bladder control, and cardiovascular function.[rx] Norepinephrine is a monoamine that is synthesized in the central nervous system and sympathetic nerves. The locus coeruleus of the brain plays a vital role in the signaling of norepinephrine. The release of norepinephrine in the brain exerts effects on a variety of processes, including stress, sleep, attention, focus, and inflammation. It also plays a role in modulating the responses of the autonomic nervous system.[rx] Histamine is another neurotransmitter that mediates homeostatic functions in the body, promotes wakefulness, modulates feeding behavior, and controls motivational behavior.[rx]
Here are a few examples of important neurotransmitter actions:
- Glutamate – is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are “modifiable”, i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can overstimulate the brain and lead to excitotoxicity causing cell death resulting in seizures or strokes.[rx] Excitotoxicity has been implicated in certain chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington disease, and Parkinson’s disease.[rx]
- GABA – is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA.[rx] Correspondingly, glycine is the inhibitory transmitter in the spinal cord.
- Acetylcholine – was the first neurotransmitter discovered in the peripheral and central nervous systems. It activates skeletal muscles in the somatic nervous system and may either excite or inhibit internal organs in the autonomic system.[rx] It is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poison curare acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain but using different types of receptors, including nicotinic and muscarinic receptors.[rx]
- Dopamine – has a number of important functions in the brain; this includes regulation of motor behavior, pleasures related to motivation, and also emotional arousal. It plays a critical role in the reward system; Parkinson’s disease has been linked to low levels of dopamine and schizophrenia has been linked to high levels of dopamine.[rx]
- Serotonin – is a monoamine neurotransmitter. Most are produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behavior, muscle contraction, and function of the cardiovascular system and endocrine system. It is speculated to have a role in depression, as some depressed patients are seen to have lower concentrations of metabolites of serotonin in their cerebrospinal fluid and brain tissue.[rx]
- Norepinephrine – which is synthesized in the central nervous system and sympathetic nerves, modulates the responses of the autonomic nervous system, sleep patterns, focus, and alertness. It is synthesized from tyrosine.
- Epinephrine – which is also synthesized from tyrosine is released in the adrenal glands and the brainstem. It plays a role in sleep, with one’s ability to become and stay alert, and the fight-or-flight response.
- Histamine – works with the central nervous system (CNS), specifically the hypothalamus (tuberomammillary nucleus) and CNS mast cells.
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