Editing Metabotropic receptor

{{short description|Type of membrane receptor that acts through a second messenger}}
{{Use mdy dates|date=October 2020}}A '''metabotropic receptor''', also referred to by the broader term [[G-protein-coupled receptor]],<ref name="Purves_2018">{{cite book | editor =Purves, Dale  | title = Neuroscience, 6th ed. |page=103 | publisher = Sinauer Associates | location = Sunderland, Mass | year = 2018 }}</ref> is a type of membrane receptor that initiates a number of [[Metabolic pathway|metabolic steps]] to modulate cell activity. The [[nervous system]] utilizes two types of [[Receptor (biochemistry)|receptors]]: '''metabotropic''' and [[Ligand-gated ion channel|ionotropic]] receptors. While ionotropic receptors form an [[Ion channel|ion channel pore]], metabotropic receptors are indirectly linked with ion channels through signal transduction mechanisms, such as [[G protein]]s.  These two types of receptors, along with their number and activity level, form the basis of the sympathetic and parasympathetic nervous systems and play key roles in regulating rates of resting energy expenditure (REE), resting heart rate, heart rate variability, and global myocardial oxygen consumption.

Both receptor types are activated by specific [[Ligand (biochemistry)|chemical ligands]]. When an ionotropic receptor is activated, it opens a channel that allows ions such as [[Sodium|Na<sup>+</sup>]], [[Potassium|K<sup>+</sup>]], or [[Chloride|Cl<sup>−</sup>]] to flow. In contrast, when a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ion channels opening or other intracellular events, but involve a range of [[second messenger]] chemicals.<ref name="Purves_2001" />

== Mechanism ==
[[Neurotransmitter|Chemical messengers]] bind to metabotropic receptors to initiate a diversity of effects caused by biochemical [[Signal transduction|signaling cascades]]. G protein-coupled receptors are all metabotropic receptors. When a ligand binds to a G protein-coupled receptor, a [[G protein-coupled receptor|guanine nucleotide-binding protein]], or [[G protein]], activates a second messenger cascade which can alter [[Transcription (biology)|gene transcription]], regulate other proteins in the cell, release [[Calcium in biology|intracellular Ca<sup>2+</sup>]], or directly affect ion channels on the membrane.<ref name=":0" /><ref>{{Citation|last=Ferguson|first=Duncan C.|title=Chapter 4 - Principles of Pharmacodynamics and Toxicodynamics|date=2018-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780128098417000046|work=Fundamentals of Toxicologic Pathology (Third Edition)|pages=47–58|editor-last=Wallig|editor-first=Matthew A.|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-809841-7.00004-6|isbn=978-0-12-809841-7|access-date=2020-10-30|editor2-last=Haschek|editor2-first=Wanda M.|editor3-last=Rousseaux|editor3-first=Colin G.|editor4-last=Bolon|editor4-first=Brad|url-access=subscription}}</ref> These receptors can remain open from seconds to minutes and are associated with long-lasting effects, such as modifying synaptic strength and modulating short- and long-term synaptic plasticity.<ref name=":1" />

Metabotropic receptors have a diversity of ligands, including but not limited to: small molecule transmitters, [[Monoamine neurotransmitter|monoamines]], [[Peptide hormone|peptides]], [[hormone]]s, and even gases.<ref name=":1" /><ref name="oxford.universitypressscholarship" /><ref name="Neuron" /> In comparison to fast-acting [[neurotransmitter]]s, these ligands are not taken up again or degraded quickly. They can also enter the [[circulatory system]] to globalize a signal.<ref name=":0" /> Most metabotropic ligands have unique receptors. Some examples include:  [[metabotropic glutamate receptor]]s, [[muscarinic acetylcholine receptor]]s, [[GABA-B receptor|GABA<sub>B</sub> receptors.]]<ref name="Purves_2001" /><ref name="Austin_2004" />

== Structure ==
The G protein-coupled receptors have seven hydrophobic transmembrane domains.  Most of them are monomeric proteins, although GABA<sub>B</sub> receptors require heterodimerization to function properly. The protein's [[N terminus]] is located on the extracellular side of the membrane and its C terminus is on the intracellular side.<ref name="Purves_2001" />

The 7 transmembrane spanning domains, with an external amino terminus, are often claimed as being alpha helix shaped, and the polypeptide chain is said to be composed of around 450&ndash;550 amino acids.

== References ==
{{reflist|refs=
<ref name="Purves_2001">{{cite book |author1=Williams, S. J. |author2=Purves, Dale | title = Neuroscience | publisher = Sinauer Associates | location = Sunderland, Mass | year = 2001 | isbn = 0-87893-742-0 }}</ref>
<ref name="Austin_2004">{{cite book | vauthors = Hoehn K, Marieb EN | title = Human Anatomy & Physiology | publisher = Pearson Benjamin Cummings | location = San Francisco | year = 2007 | isbn = 978-0-8053-5910-7 | chapter-url = http://wps.aw.com/bc_marieb_happlace_7_oa/42/10967/2807754.cw/index.html | chapter = Fundamentals of the nervous system and nervous tissue | url = https://archive.org/details/humananatomyphys00mari_4}}</ref>
<ref name=":0">{{Citation|chapter=Principles of Neural Design|date=2015|chapter-url=http://dx.doi.org/10.7551/mitpress/9395.003.0019|publisher=The MIT Press|doi=10.7551/mitpress/9395.003.0019|isbn=978-0-262-32731-2|access-date=2020-10-18 }}</ref>
<ref name=":1">{{Cite journal|last1=Nadim|first1=Farzan|last2=Bucher|first2=Dirk|date=December 2014|title=Neuromodulation of Neurons and Synapses|journal=Current Opinion in Neurobiology|volume=29|pages=48–56|doi=10.1016/j.conb.2014.05.003|issn=0959-4388|pmc=4252488|pmid=24907657}}</ref>
<ref name="oxford.universitypressscholarship">{{cite book |last1=Burrows |first1=Malcolm |title=The Neurobiology of an Insect Brain |date=1996 |publisher=Oxford Scholarship |isbn=9780198523444 |url=https://oxford.universitypressscholarship.com/view/10.1093/acprof:oso/9780198523444.001.0001/acprof-9780198523444-chapter-5 |chapter=Neurotransmitters, neuromodulators and neurohormones|doi=10.1093/acprof:oso/9780198523444.003.0005|url-access=subscription}}</ref>
<ref name="Neuron">{{Cite journal|last=Marder|first=Eve|date=2012-10-04|title=Neuromodulation of Neuronal Circuits: Back to the Future|journal=Neuron|volume=76|issue=1|pages=1–11|doi=10.1016/j.neuron.2012.09.010|issn=0896-6273|pmc=3482119|pmid=23040802}}</ref>
}}

== Further reading ==
{{refbegin}}
* Zimmerberg, B.  2002.  Dopamine receptors: A representative family of metabotropic receptors. Multimedia Neuroscience Education Project [http://www.williams.edu/imput/IIIB1.html]
{{refend}}

{{G protein-coupled receptors}}
{{Tyrosine kinases}}

[[Category:G protein-coupled receptors]]
[[Category:Neurochemistry]]
[[Category:Signal transduction]]
[[Category:Transmembrane receptors]]