Editing Neurotransmitter (section)

==Mechanism and cycle==
{{See also|Neurotransmission}}

===Synthesis===

Neurotransmitters are generally synthesized in neurons and are made up of, or derived from, precursor molecules that are found abundantly in the cell. Classes of neurotransmitters include [[amino acid]]s, [[monoamines]], and [[peptide]]s. Monoamines are synthesized by altering a single amino acid. For example, the precursor of serotonin is the amino acid tryptophan. Peptide neurotransmitters, or [[neuropeptide]]s, are protein transmitters which are larger than the classical small-molecule neurotransmitters and are often released together to elicit a modulatory effect.<ref>{{Cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM |date=2001| chapter = Peptide Neurotransmitters | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK10873/ | title = Neuroscience |publisher=Sinauer Associates | edition = 2nd }}</ref> Purine neurotransmitters, like [[Adenosine triphosphate|ATP]], are derived from nucleic acids. Metabolic products such as [[nitric oxide]] and [[carbon monoxide]] have also been reported to act like neurotransmitters.<ref>{{Cite journal |last1=Xue |first1=L. |last2=Farrugia |first2=G. |last3=Miller |first3=S. M. |last4=Ferris |first4=C. D. |last5=Snyder |first5=S. H. |last6=Szurszewski |first6=J. H. |date=2000-02-15 |title=Carbon monoxide and nitric oxide as coneurotransmitters in the enteric nervous system: Evidence from genomic deletion of biosynthetic enzymes |journal=Proceedings of the National Academy of Sciences |language=en |volume=97 |issue=4 |pages=1851–1855 |doi=10.1073/pnas.97.4.1851 |doi-access=free |issn=0027-8424 |pmc=26525 |pmid=10677545|bibcode=2000PNAS...97.1851X }}</ref>
{| class="wikitable"
!
!Examples
|-
|Amino acids
|[[glycine]], [[glutamate]]
|-
|Monoamines
|[[serotonin]], [[epinephrine]], [[dopamine]]
|-
|Peptides
|[[substance P]], [[opioid]]s
|-
|Purines
|[[Adenosine triphosphate|ATP]], [[Guanosine triphosphate|GTP]]
|-
|Other
|[[nitric oxide]], [[carbon monoxide]]
|}

===Storage===

[[File:Neurotransmitters.jpg|thumb|Synaptic vesicles containing neurotransmitters]]
Neurotransmitters are generally stored in [[synaptic vesicles]], clustered close to the [[cell membrane]] at the [[axon terminal]] of the presynaptic neuron. However, some neurotransmitters, like the metabolic gases carbon monoxide and nitric oxide, are synthesized and released immediately following an action potential without ever being stored in vesicles.<ref>{{cite journal | vauthors = Sanders KM, Ward SM | title = Nitric oxide and its role as a non-adrenergic, non-cholinergic inhibitory neurotransmitter in the gastrointestinal tract | journal = British Journal of Pharmacology | volume = 176 | issue = 2 | pages = 212–227 | date = January 2019 | pmid = 30063800 | pmc = 6295421 | doi = 10.1111/bph.14459 }}</ref>

===Release===

Generally, a neurotransmitter is released via [[exocytosis]] at the presynaptic terminal in response to an electrical signal called an [[action potential]] in the presynaptic neuron. However, low-level "baseline" release also occurs without electrical stimulation. Neurotransmitters are released into and diffuse across the [[synaptic cleft]], where they bind to specific [[Receptor (biochemistry)|receptors]] on the membrane of the postsynaptic neuron.<ref>{{cite book | vauthors = Elias LJ, Saucier DM | date =2005 | title = Neuropsychology: Clinical and Experimental Foundations. | location = Boston | publisher = Pearson }}</ref>

===Receptor interaction===

After being released into the synaptic cleft, neurotransmitters diffuse across the synapse where they are able to interact with receptors on the target cell. The effect of the neurotransmitter is dependent on the identity of the target cell's receptors present at the synapse. Depending on the receptor, binding of neurotransmitters may cause [[Excitatory synapse|excitation]], [[Inhibitory postsynaptic potential|inhibition]], or modulation of the postsynaptic neuron.<ref name=":1" />

===Elimination===
[[File:Synapse acetylcholine.png|thumb|Acetylcholine is cleaved in the synaptic cleft into acetic acid and choline.]]

In order to avoid continuous activation of receptors on the post-synaptic or target cell, neurotransmitters must be removed from the synaptic cleft.<ref>{{cite journal | vauthors = Chergui K, Suaud-Chagny MF, Gonon F | title = Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo | journal = Neuroscience | volume = 62 | issue = 3 | pages = 641–645 | date = October 1994 | pmid = 7870295 | doi = 10.1016/0306-4522(94)90465-0 | s2cid = 20465561 }}</ref>  Neurotransmitters are removed through one of three mechanisms:

# Diffusion – neurotransmitters drift out of the synaptic cleft, where they are absorbed by [[glial cells]]. These glial cells, usually [[astrocyte]]s, absorb the excess neurotransmitters.
#* Astrocytes, a type of [[glia]]l cell in the brain, actively contribute to synaptic communication through astrocytic diffusion or [[Gliotransmitter|gliotransmission]]. Neuronal activity triggers an increase in astrocytic calcium levels, prompting the release of gliotransmitters, such as [[Glutamate (neurotransmitter)|glutamate]], ATP, and D-serine. These gliotransmitters diffuse into the [[Extracellular fluid|extracellular]] space, interacting with nearby neurons and influencing synaptic transmission. By regulating extracellular neurotransmitter levels, astrocytes help maintain proper synaptic function. This bidirectional communication between astrocytes and neurons add complexity to brain signaling, with implications for brain function and neurological disorders.<ref>{{Cite journal |last1=Mustafa |first1=Asif K. |last2=Kim |first2=Paul M. |last3=Snyder |first3=Solomon H. |date=August 2004 |title=D-Serine as a putative glial neurotransmitter |journal=Neuron Glia Biology |language=en |volume=1 |issue=3 |pages=275–281 |doi=10.1017/S1740925X05000141 |pmid=16543946 |pmc=1403160 |issn=1741-0533}}</ref><ref>{{Cite journal |last1=Wolosker |first1=Herman |last2=Dumin |first2=Elena |last3=Balan |first3=Livia |last4=Foltyn |first4=Veronika N. |date=July 2008 |title=d-Amino acids in the brain: d-serine in neurotransmission and neurodegeneration: d-Serine in neurotransmission and neurodegeneration |journal=FEBS Journal |language=en |volume=275 |issue=14 |pages=3514–3526 |doi=10.1111/j.1742-4658.2008.06515.x|pmid=18564180 |s2cid=25735605 |doi-access=free }}</ref>
# Enzyme degradation – proteins called [[enzymes]] break the neurotransmitters down.
# [[Reuptake]] – neurotransmitters are reabsorbed into the pre-synaptic neuron. Transporters, or [[membrane transport protein]]s, pump neurotransmitters from the synaptic cleft back into [[axon terminal]]s (the presynaptic neuron) where they are stored for reuse.

For example, [[acetylcholine]] is eliminated by having its acetyl group cleaved by the enzyme [[acetylcholinesterase]]; the remaining [[choline]] is then taken in and recycled by the pre-synaptic neuron to synthesize more [[acetylcholine]].<ref>{{cite journal | vauthors = Thapa S, Lv M, Xu H | title = Acetylcholinesterase: A Primary Target for Drugs and Insecticides | journal = Mini Reviews in Medicinal Chemistry | volume = 17 | issue = 17 | pages = 1665–1676 | date = 2017-11-30 | pmid = 28117022 | doi = 10.2174/1389557517666170120153930 }}</ref> Other neurotransmitters are able to [[Diffusion|diffuse]] away from their targeted synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at regulatory points, which may be targeted by the body's regulatory system or medication. [[Cocaine]] blocks a dopamine transporter responsible for the reuptake of dopamine. Without the transporter, dopamine diffuses much more slowly from the synaptic cleft and continues to activate the dopamine receptors on the target cell.<ref>{{cite journal | vauthors = Vasica G, Tennant CC | title = Cocaine use and cardiovascular complications | journal = The Medical Journal of Australia | volume = 177 | issue = 5 | pages = 260–262 | date = September 2002 | pmid = 12197823 | doi = 10.5694/j.1326-5377.2002.tb04761.x | s2cid = 18572638 }}</ref>