Neurotransmitters in the context of Biosynthetic


Neurotransmitters in the context of Biosynthetic

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⭐ Core Definition: Neurotransmitters

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

Neurotransmitters are released from synaptic vesicles into the synaptic cleft where they are able to interact with neurotransmitter receptors on the target cell. Some neurotransmitters are also stored in large dense core vesicles. The neurotransmitter's effect on the target cell is determined by the receptor it binds to. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available and often require a small number of biosynthetic steps for conversion.

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Neurotransmitters in the context of Enteric nervous system

The enteric nervous system (ENS) is one of the three divisions of the autonomic nervous system (ANS), the others being the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). It consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. The ENS is nicknamed the "second brain". It is derived from neural crest cells.

The enteric nervous system is capable of operating independently of the brain and spinal cord, but is thought to rely on innervation from the vagus nerve and prevertebral ganglia in healthy subjects. However, studies have shown that the system is operable with a severed vagus nerve. The neurons of the enteric nervous system control the motor functions of the system, in addition to the secretion of gastrointestinal enzymes. These neurons communicate through many neurotransmitters similar to the CNS, including acetylcholine, dopamine, and serotonin. The large presence of serotonin and dopamine in the intestines are key areas of research for neurogastroenterology.

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Neurotransmitters in the context of Neuropeptides

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

Neuropeptides are synthesized from large precursor proteins which are cleaved and post-translationally processed then packaged into large dense core vesicles. Neuropeptides are often co-released with other neuropeptides and neurotransmitters in a single neuron, yielding a multitude of effects. Once released, neuropeptides can diffuse widely to affect a broad range of targets.

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Neurotransmitters in the context of Extracellular space

Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells.

The composition of the extracellular space includes metabolites, ions, proteins, and many other substances that might affect cellular function. For example, neurotransmitters "jump" from cell to cell to facilitate the transmission of an electric current in the nervous system. Hormones also act by travelling the extracellular space towards cell receptors.

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Neurotransmitters in the context of Axon terminal

Axon terminals (also called terminal boutons, synaptic boutons, end-feet, or presynaptic terminals) are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body to transmit those impulses to other neurons, muscle cells, or glands. Most presynaptic terminals in the central nervous system are formed along the axons (en passant boutons), not at their ends (terminal boutons).

Functionally, the axon terminal converts an electrical signal into a chemical signal. When an action potential arrives at an axon terminal (A), the neurotransmitter is released and diffuses across the synaptic cleft. If the postsynaptic cell (B) is also a neuron, neurotransmitter receptors generate a small electrical current that changes the postsynaptic potential. If the postsynaptic cell (B) is a muscle cell (neuromuscular junction), it contracts.

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Neurotransmitters in the context of Exocytosis

Exocytosis (/ˌɛkssˈtsɪs/) is a form of active transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

In exocytosis, membrane-bound secretory vesicles are carried to the cell membrane, where they dock and fuse at porosomes and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. This secretion is possible because the vesicle transiently fuses with the plasma membrane. In the context of neurotransmission, neurotransmitters are typically released from synaptic vesicles into the synaptic cleft via exocytosis; however, neurotransmitters can also be released via reverse transport through membrane transport proteins.

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Neurotransmitters in the context of Neurogastroenterology

The enteric nervous system (ENS) is one of the three divisions of the autonomic nervous system (ANS), the others being the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). The ENS is formed from the myenteric plexus, and the submucosal plexus, and consists of a mesh-like system of neurons that governs the functions of the gastrointestinal tract, including motility and secretion, and is known as the "second brain". It is derived from neural crest cells.

The enteric nervous system is capable of operating independently of the brain and spinal cord, but is thought to rely on innervation from the vagus nerve and prevertebral ganglia in healthy subjects. However, studies have shown that the system is operable with a severed vagus nerve. The neurons of the enteric nervous system control the motor functions of the system, in addition to the secretion of gastrointestinal enzymes. These neurons communicate through many neurotransmitters similar to the CNS, including acetylcholine, dopamine, and serotonin. The large presence of serotonin and dopamine in the intestines are key areas of research for neurogastroenterology.

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Neurotransmitters in the context of Neurotransmitter transporter

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

Vesicular transporters move neurotransmitters into synaptic vesicles, regulating the concentrations of substances within them. Vesicular transporters rely on a proton gradient created by the hydrolysis of adenosine triphosphate (ATP) in order to carry out their work: v-ATPase hydrolyzes ATP, causing protons to be pumped into the synaptic vesicles and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle.

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Neurotransmitters in the context of Oligodendrocyte progenitor cell

Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes and myelin. They are typically identified in the human by co-expression of PDGFRA and CSPG4.

OPCs play a critical role in developmental and adult myelinogenesis. They give rise to oligodendrocytes, which then wrap around axons and provide electrical insulation by forming a myelin sheath. This enables faster action potential propagation and high fidelity transmission without a need for an increase in axonal diameter. The loss or lack of OPCs, and consequent lack of differentiated oligodendrocytes, is associated with a loss of myelination and subsequent impairment of neurological functions. In addition, OPCs express receptors for various neurotransmitters and undergo membrane depolarization when they receive synaptic inputs from neurons.

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Neurotransmitters in the context of Subfornical organ

The subfornical organ (SFO) is one of the circumventricular organs of the brain. Its name comes from its location on the ventral surface of the fornix near the interventricular foramina (foramina of Monro), which interconnect the lateral ventricles and the third ventricle. Like all circumventricular organs, the subfornical organ is well-vascularized, and like all circumventricular organs except the subcommissural organ, some SFO capillaries have fenestrations, which increase capillary permeability. The SFO is considered a sensory circumventricular organ because it is responsive to a wide variety of hormones and neurotransmitters, as opposed to secretory circumventricular organs, which are specialized in the release of certain substances.

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Neurotransmitters in the context of Non-proteinogenic amino acids

In biochemistry, non-coded or non-proteinogenic amino acids are distinct from the 22 proteinogenic amino acids (21 in eukaryotes), which are naturally encoded in the genome of organisms for the assembly of proteins. However, over 140 non-proteinogenic amino acids occur naturally in proteins (but not included in the genetic code) and thousands more may occur in nature or be synthesized in the laboratory. Chemically synthesized amino acids are often referred to as unnatural or non-canonical amino acids. Unnatural amino acids can be synthetically prepared from their native analogs via modifications such as amine alkylation, side chain substitution, structural bond extension cyclization, and isosteric replacements within the amino acid backbone. Many non-proteinogenic amino acids are important:

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Neurotransmitters in the context of Baclofen

Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity, such as from a spinal cord injury or multiple sclerosis. Baclofen is a potent muscle relaxant and GABA agonist. It may also be used for hiccups and muscle spasms near the end of life, and off-label to treat alcohol use disorder or opioid withdrawal symptoms. It is taken orally or by intrathecal pump (delivered into the spinal canal via an implantable pump device). It is sometimes used transdermally (applied topically to the skin) in combination with gabapentin and clonidine prepared at a compounding pharmacy. It is believed to work by decreasing levels of certain neurotransmitters.

Baclofen should be avoided in the setting of chronic kidney disease and end stage renal disease as even small doses can cause excessive toxicity. Common side effects include sleepiness, weakness, and dizziness. Serious side effects, such as seizures and rhabdomyolysis, may occur if use of baclofen is stopped abruptly. Use during pregnancy is of unclear safety, whilst use during breastfeeding is likely safe, and even more so if oral administration is avoided.

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