View source for Neurotransmitter receptor

{{Short description|Type of protein}}
[[File:PDB 1hzx 7TM Sketch Membrane.png|thumb|300px|Figure 1. The seven transmembrane α-helix structure of a G-protein-coupled receptor.]]

A '''neurotransmitter receptor''' (also known as a '''neuroreceptor''') is a membrane [[receptor protein]]<ref name="Levitan 2002">{{cite book|last=Levitan|first=Irwin B.|author2=Leonard K. Kaczmarek |title=The Neuron|publisher=Oxford University Press|year=2002|edition= Third pg. 285}}</ref> that is activated by a [[neurotransmitter]].<ref name="brainexplorer.org">{{cite web|url=http://www.brainexplorer.org/neurological_control/neurological_neurotransmitters.shtml |title=Neurological Control - Neurotransmitters |publisher=Brain Explorer |date=2011-12-20 |access-date=2012-11-04}}</ref> Chemicals on the outside of the cell, such as a neurotransmitter, can bump into the cell's membrane, in which there are receptors. If a neurotransmitter bumps into its corresponding receptor, they will bind and can trigger other events to occur inside the cell. Therefore, a membrane [[Receptor (biochemistry)|receptor]] is part of the molecular machinery that allows cells to  [[Cell communication|communicate]] with one another. A neurotransmitter receptor is a class of receptors that specifically binds with neurotransmitters as opposed to other molecules.

In [[postsynaptic]] cells, neurotransmitter receptors receive signals that trigger an electrical signal,  by regulating the activity of [[ion channel]]s. The influx of ions through ion channels opened due to the binding of neurotransmitters to specific receptors can change the membrane potential of a neuron.  This can result in a signal that runs along the [[axon]] (see [[action potential]]) and is passed along at a synapse to another neuron and possibly on to a [[Biological neural network|neural network]].<ref name="Levitan 2002"/> On [[presynaptic]] cells, there are receptors known as [[autoreceptor]]s that are specific to the neurotransmitters released by that cell, which provide feedback and mediate excessive neurotransmitter release from it.<ref>{{cite web|url=http://www.rndsystems.com/molecule_group.aspx?g=682&r=9|title= Neurotransmitter Receptors, Transporters, & Ion Channels|publisher=www.rndsystems.com}}</ref>

There are two major types of neurotransmitter receptors: ''ionotropic'' and ''metabotropic''. [[Ligand-gated ion channel|Ionotropic]] means that ions can pass through the receptor, whereas [[Metabotropic receptor|metabotropic]] means that a second messenger inside the cell relays the message (i.e. metabotropic receptors do not have channels). There are several kinds of metabotropic receptors, including [[G protein-coupled receptor]]s.<ref name="brainexplorer.org"/><ref>{{cite web|url=http://web.williams.edu/imput/synapse/pages/III.html |title=3. Neurotransmitter Postsynaptic Receptors |publisher=Web.williams.edu |access-date=2012-11-04}}</ref> Ionotropic receptors are also called [[ligand-gated ion channels]] and they can be activated by neurotransmitters ([[ligand]]s) like [[Glutamate receptor|glutamate]] and [[GABAA receptor|GABA]], which then [[Ion channel|allow specific ions]] through the membrane.  Sodium ions (that are, for example, allowed passage by the [[AMPA receptor|glutamate receptor]]) [[Excitatory postsynaptic potential|excite]] the post-synaptic cell, while chloride ions (that are, for example, allowed passage by the [[GABAA receptor|GABA receptor)]] [[Inhibitory postsynaptic potential|inhibit]] the post-synaptic cell. Inhibition reduces the chance that an [[action potential]] will occur, while excitation increases the chance.  Conversely, G-protein-coupled receptors are neither excitatory nor inhibitory. Rather, they can have a broad number of functions such as modulating the actions of excitatory and inhibitory ion channels or triggering a signalling cascade that releases calcium from stores inside the cell.<ref name="brainexplorer.org"/> Most neurotransmitters receptors are G-protein coupled.<ref name="Levitan 2002"/>

==Localization==

Neurotransmitter (NT) receptors are located on the surface of [[neuron]]al and [[glia]]l [[Cell (biology)|cells]]. At a [[synapse]], one neuron sends messages to the other neuron via neurotransmitters. Therefore, the postsynaptic neuron, the one receiving the message, clusters NT receptors at this specific place in its membrane. NT receptors can be inserted into any region of the neuron's membrane such as dendrites, axons, and the cell body.<ref>{{Cite book|title=Neuroscience : exploring the brain|last=F.|first=Bear, Mark|date=2007|publisher=Lippincott Williams & Wilkins|others=Connors, Barry W., Paradiso, Michael A.|isbn=9780781760034|edition=3rd|location=Philadelphia, PA|pages=[https://archive.org/details/neuroscienceexpl00mark/page/106 106]|oclc=62509134|url=https://archive.org/details/neuroscienceexpl00mark/page/106}}</ref> Receptors can be located in different parts of the body to act as either an inhibitor or an excitatory receptor for a specific Neurotransmitter <ref name="med.stanford.edu">Goldman, B. (2010, November 17). New imaging method developed at Stanford reveals stunning details of brain connections. In Stanford medicine news center. Retrieved from https://med.stanford.edu/news/all-news/2010/11/new-imaging-method-developed-at-stanford-reveals-stunning-details-of-brain-connections.html.</ref> An example of this are the receptors for the neurotransmitter Acetylcholine (ACh), one  receptor is located at the neuromuscular junction in skeletal muscle to facilitate muscle contraction (excitation), while the other receptor is located in the heart to slow down heart rate (inhibitory) <ref name="med.stanford.edu"/>

==Ionotropic receptors: neurotransmitter-gated ion channels==

[[Image:LGIC.png|thumb|Ligand-gated ion channel]]

'''[[Ligand-gated ion channels]]''' ('''LGICs''') are one type of ionotropic receptor or [[Ion channel linked receptors|channel-linked receptor]].  They are a group of [[transmembrane]] [[ion channel]]s that are opened or closed in response to the binding of a chemical messenger (i.e., a [[ligand (biochemistry)|ligand]]),<ref>{{DorlandsDict|two/000019817|ligand-gated channel}}</ref> such as a [[neurotransmitter]].<ref name="Purves" >{{cite book | author = Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White | title = Neuroscience. 4th ed. | publisher = Sinauer Associates | pages = 156–7 | year = 2008 | isbn = 978-0-87893-697-7}}</ref>

The binding site of [[Endogeny#Biology|endogenous]] ligands on LGICs protein complexes are normally located on a different portion of the protein (an [[allosteric regulation|allosteric]] binding site) compared to where the ion conduction pore is located. The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of [[metabotropic receptor]]s, which use [[Second messenger system|second messenger]]s. LGICs are also different from [[voltage-gated ion channel]]s (which open and close depending on [[membrane potential]]), and [[stretch-activated ion channel]]s (which open and close depending on mechanical deformation of the [[cell membrane]]).<ref name="Purves" /><ref name="pmid15157178">{{cite journal |vauthors=Connolly CN, Wafford KA | title = The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function | journal = Biochem. Soc. Trans. | volume = 32 | issue = Pt3 | pages = 529–34 | year = 2004 | pmid = 15157178 | doi = 10.1042/BST0320529 | s2cid = 9115777 }}</ref>

==Metabotropic receptors: G-protein coupled receptors==
[[Image:Mu-opioid receptor (GPCR).png|thumb|A [[opioid receptor|mu-opioid G-protein-coupled receptor]] with its agonist]]

'''[[G protein-coupled receptors]]''' ('''GPCRs'''), also known as '''seven-transmembrane domain receptors''', '''7TM receptors''', '''heptahelical receptors''', '''serpentine receptor''', and '''G protein-linked receptors''' ('''GPLR'''), comprise a large [[protein]] family of [[membrane receptor|transmembrane receptor]]s that sense [[molecule]]s outside the [[Cell (biology)|cell]] and activate inside [[signal transduction]] pathways and, ultimately, cellular responses. G protein-coupled receptors are found only in [[eukaryote]]s, including yeast,  [[choanoflagellate]]s,<ref name="pmid12869759">{{cite journal |vauthors=King N, Hittinger CT, Carroll SB | title = Evolution of key cell signaling and adhesion protein families predates animal origins | journal = Science | volume = 301 | issue = 5631 | pages = 361–3 | year = 2003 | pmid = 12869759 | doi = 10.1126/science.1083853 | bibcode = 2003Sci...301..361K | s2cid = 9708224 }}</ref> and animals. The [[Ligand (biochemistry)|ligands]] that bind and activate these receptors include light-sensitive compounds, [[odor]]s, [[pheromone]]s, [[hormone]]s, and [[neurotransmitter]]s, and vary in size from small molecules to [[peptide]]s to large [[protein]]s. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs.<ref>{{cite journal | first=David | last=Filmore | pages=24–28 | title=It's a GPCR world | journal=Modern Drug Discovery | volume=2004 | year=2004 | issue=November | url=http://pubs.acs.org/subscribe/journals/mdd/v07/i11/html/1104feature_filmore.html}}</ref><ref name="pmid17139284">{{cite journal |vauthors=Overington JP, Al-Lazikani B, Hopkins AL | title = How many drug targets are there? | journal = Nat Rev Drug Discov | volume = 5 | issue = 12 | pages = 993–6 |date=December 2006 | pmid = 17139284 | doi = 10.1038/nrd2199 | s2cid = 11979420 }}</ref>

There are two principal signal transduction pathways involving the G protein-coupled receptors: the [[Cyclic adenosine monophosphate|cAMP]] signal pathway and the [[phosphatidylinositol]] signal pathway.<ref name="Gilman A.G. 1987 615–649">{{cite journal | author = Gilman A.G. | title = G Proteins: Transducers of Receptor-Generated Signals | journal = Annual Review of Biochemistry | year=1987 | volume=56 | pages=615–649 | doi = 10.1146/annurev.bi.56.070187.003151 | pmid = 3113327| s2cid = 33992382 }}</ref> When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a [[guanine nucleotide exchange factor]] (GEF). The GPCR can then activate an associated [[G-protein]] by exchanging its bound [[guanosine diphosphate|GDP]] for a [[guanosine triphosphate|GTP]]. The G-protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type ([[Gαs|G<sub>αs</sub>]], [[Gαi|G<sub>αi/o</sub>]], [[Gαq|G<sub>αq/11</sub>]], [[G12/G13 alpha subunits|G<sub>α12/13</sub>]]).<ref name="Wettschureck_2005">{{cite journal |vauthors=Wettschureck N, Offermanns S | title = Mammalian G proteins and their cell type specific functions | journal = Physiol. Rev. | volume = 85 | issue = 4 | pages = 1159–204 |date=October 2005 | pmid = 16183910 | doi = 10.1152/physrev.00003.2005 | s2cid = 24270725 }}</ref>{{rp|1160}}

==Desensitization and neurotransmitter concentration==

Neurotransmitter receptors are subject to ligand-induced desensitization: That is, they can become unresponsive upon prolonged exposure to their neurotransmitter. Neurotransmitter receptors are present on both [[postsynaptic]] neurons ''and'' presynaptic neurons with the former being used to receive [[neurotransmitter]]s and the latter for the purpose of preventing further release of a given neurotransmitter.<ref name="web.indstate">{{cite web |url=http://web.indstate.edu/thcme/mwking/nerves.html#table |title=THE Medical Biochemistry Page |publisher=Web.indstate.edu |access-date=2012-11-04 |archive-date=2019-01-10 |archive-url=https://web.archive.org/web/20190110235459/http://web.indstate.edu/thcme/mwking/nerves.html#table |url-status=dead }}</ref> In addition to being found in neuron cells, neurotransmitter receptors are also found in various immune and muscle tissues. Many neurotransmitter receptors are categorized as a [[serpentine receptor]] or [[G protein-coupled receptor]] because they span the cell membrane not once, but seven times. Neurotransmitter receptors are known to become unresponsive to the type of [[neurotransmitter]] they receive when exposed for extended periods of time. This phenomenon is known as ligand-induced desensitization<ref name="web.indstate" /> or [[downregulation]].

==Example neurotransmitter receptors==

The following are some major classes of neurotransmitter receptors:<ref>ed. Kebabain, J. W. & Neumeyer, J. L. (1994). "RBI Handbook of Receptor Classification"</ref>
*[[Adrenergic receptor|Adrenergic]]:   α<sub>1A</sub>, α<sub>1b</sub>, α<sub>1c</sub>, α<sub>1d</sub>,   α<sub>2a</sub>, α<sub>2b</sub>, α<sub>2c</sub>, α<sub>2d</sub>,   β<sub>1</sub>, β<sub>2</sub>, β<sub>3</sub>
*[[Acetylcholine receptor|Cholinergic]]:
**[[Muscarinic acetylcholine receptor|Muscarinic]]: M1, M2, M3, M4, M5
**[[Nicotinic acetylcholine receptor|Nicotinic]]: muscle, neuronal (α-bungarotoxin-insensitive), neuronal (α-bungarotoxin-sensitive)
*[[Dopamine receptor|Dopaminergic]]:   [[Dopamine receptor D1|D<sub>1</sub>]], [[Dopamine receptor D2|D<sub>2</sub>]], [[Dopamine receptor D3|D<sub>3</sub>]], [[Dopamine receptor D4|D<sub>4</sub>]], [[Dopamine receptor D5|D<sub>5</sub>]]
*[[GABA receptor|GABAergic]]:   [[GABAA|GABA<sub>A</sub>]], [[GABAB|GABA<sub>B1a</sub>]], [[GABAB|GABA<sub>B1δ</sub>]], [[GABAB|GABA<sub>B2</sub>]], [[GABAA-rho|GABA<sub>C</sub>]]
*[[Glutamate receptor|Glutamatergic]]:   [[NMDA receptor|NMDA]], [[AMPA receptor|AMPA]], [[Kainate receptor|Kainate]], mGluR<sub>1</sub>, mGluR<sub>2</sub>, mGluR<sub>3</sub>, mGluR<sub>4</sub>, mGluR<sub>5</sub>, mGluR<sub>6</sub>, mGluR<sub>7</sub>
*[[Glycine receptor|Glycinergic]]:   Glycine
*[[Histamine receptor|Histaminergic]]:   H<sub>1</sub>, H<sub>2</sub>, H<sub>3</sub>
*[[Opioid receptor|Opioidergic]]:   [[Mu Opioid receptor|μ]], [[Delta Opioid receptor|δ<sub>1</sub>]], [[Delta Opioid receptor|δ<sub>2</sub>]], [[Kappa Opioid receptor|κ]]
*[[5-HT receptor|Serotonergic]]:   [[5-HT1A|5-HT<sub>1A</sub>]], [[5-HT1B|5-HT<sub>1B</sub>]], [[5-HT1D|5-HT<sub>1D</sub>]], [[5-HT1E|5-HT<sub>1E</sub>]], [[5-HT1F|5-HT<sub>1F</sub>]], [[5-HT2A|5-HT<sub>2A</sub>]], [[5-HT2B|5-HT<sub>2B</sub>]], [[5-HT2C|5-HT<sub>2C</sub>]], [[5-HT3|5-HT<sub>3</sub>]], [[5-HT4|5-HT<sub>4</sub>]], [[5-HT5|5-HT<sub>5</sub>]], [[5-HT6|5-HT<sub>6</sub>]], [[5-HT7|5-HT<sub>7</sub>]]

==See also==
{{col div|colwidth=35em}}
* [[Autoreceptor]]
* [[Catecholamines]]
* [[Cholinergic]] [[agonists]] and [[Receptor antagonist|antagonists]]
* [[Heteroreceptor]]
* [[Imidazoline receptor]]
* [[Neuromuscular transmission]]
* [[Synaptic transmission]]
{{Div col end}}

==Notes and references==
{{Reflist}}

==External links==
* [http://www.brainexplorer.org/neurological_control/neurological_neurotransmitters.shtml Brain Explorer]
* [http://web.williams.edu/imput/synapse/pages/III.html Neurotransmitters Postsynaptic Receptors]
*[http://www.jneurosci.org/content/29/41/12717.full Snyder (2009) Neurotransmitters, Receptors, and Second Messengers Galore in 40 Years. Journal of Neuroscience. 29(41): 12717-12721.]
*[http://www.annualreviews.org/doi/abs/10.1146/annurev.ph.38.030176.001101 Snyder and Bennett (1976) Neurotransmitter Receptors in the Brain: Biochemical Identification. Annual Review of Physiology. Vol. 38: 153-175]
*[http://faculty.washington.edu/chudler/chnt1.html Neuroscience for Kids: Neurotransmitters]
*[http://id.loc.gov/authorities/sh85091182 Library of Congress Authorities and Vocabularies: Neurotransmitter Receptors]
*[http://www.rndsystems.com/molecule_group.aspx?g=682&r=9 Neurotransmitter Receptors, Transporters, & Ion Channels]
* {{MeshName|Neuroregulator+Receptor}}

{{Transmembrane receptors}}
{{G protein-coupled receptors}}
{{Authority control}}

{{DEFAULTSORT:Neurotransmitter Receptor}}
[[Category:Receptors]]
[[Category:Neurochemistry]]