Editing Serotonin (section)

====Serotonylation====
{{Main|Serotonylation}}

Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins.<ref name="pmid19859528"/> This process underlies serotonin's effects upon platelet-forming cells ([[thrombocyte]]s) in which it links to the modification of signaling enzymes called [[GTPase]]s that then trigger the release of vesicle contents by [[exocytosis]].<ref name="pmid14697203">{{cite journal | vauthors = Walther DJ, Peter JU, Winter S, Höltje M, Paulmann N, Grohmann M, Vowinckel J, Alamo-Bethencourt V, Wilhelm CS, Ahnert-Hilger G, Bader M | title = Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release | journal = Cell | volume = 115 | issue = 7 | pages = 851–862 | date = December 2003 | pmid = 14697203 | doi = 10.1016/S0092-8674(03)01014-6 | s2cid = 16847296 | doi-access = free }}</ref> A similar process underlies the pancreatic release of insulin.<ref name="pmid19859528"/>

The effects of serotonin upon vascular smooth [[muscle tone]]{{snd}}the biological function after which serotonin was originally named{{snd}}depend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.<ref name="pmid19479059">{{cite journal | vauthors = Watts SW, Priestley JR, Thompson JM | title = Serotonylation of vascular proteins important to contraction | journal = PLOS ONE | volume = 4 | issue = 5 | pages = e5682 | date = May 2009 | pmid = 19479059 | pmc = 2682564 | doi = 10.1371/journal.pone.0005682 | doi-access = free | bibcode = 2009PLoSO...4.5682W }}</ref>

{| class = wikitable
|+ <big>Binding profile of serotonin</big>
! Receptor !! K<sub>i</sub> (nM)<ref>{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | url = http://pdsp.med.unc.edu/pdsp.php | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 17 December 2013 | date = 12 January 2011 | url-status = dead | archive-url = https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php | archive-date = 8 November 2013 | df = dmy-all }}</ref> !! Receptor function<ref group = Note>References for the functions of these receptors are available on the wikipedia pages for the specific receptor in question</ref>
|-
| colspan ="3" align="center" | 5-HT<sub>1</sub> receptor family signals via [[Gi alpha subunit|G<sub>i/o</sub>]] inhibition of [[adenylyl cyclase]].
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| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 3.17 || Memory{{Vague|date=March 2014}} (agonists ↓); learning{{Vague|date=March 2014}} (agonists ↓); anxiety (agonists ↓); depression (agonists ↓); positive, negative, and cognitive symptoms of schizophrenia (partial agonists ↓); analgesia (agonists ↑); [[aggression]] (agonists ↓); dopamine release in the prefrontal cortex (agonists ↑); serotonin release and synthesis (agonists ↓)
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| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 4.32 || Vasoconstriction (agonists ↑); aggression (agonists ↓); bone mass (↓). Serotonin autoreceptor.
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| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 5.03 || Vasoconstriction (agonists ↑)
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| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 7.53 ||
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| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || 10 ||
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| colspan ="3" align="center" | 5-HT<sub>2</sub> receptor family signals via [[Gq alpha subunit|G<sub>q</sub>]] activation of [[phospholipase C]].
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| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 11.55 || Psychedelia (agonists ↑); depression (agonists & antagonists ↓); anxiety (antagonists ↓); positive and negative symptoms of schizophrenia (antagonists ↓); norepinephrine release from the [[locus coeruleus]] (antagonists ↑); glutamate release in the [[prefrontal cortex]] (agonists ↑); dopamine in the prefrontal cortex (agonists ↑);<ref>{{cite journal | vauthors = Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F | title = The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity | journal = Journal of Neurochemistry | volume = 95 | issue = 6 | pages = 1597–1607 | date = December 2005 | pmid = 16277612 | doi = 10.1111/j.1471-4159.2005.03485.x | hdl-access = free | s2cid = 18350703 | hdl = 10261/33026 }}</ref> urinary bladder contractions (agonists ↑)<ref name="MoroEdwards2016">{{cite journal | vauthors = Moro C, Edwards L, Chess-Williams R | title = 5-HT<sub>2A</sub> receptor enhancement of contractile activity of the porcine urothelium and lamina propria | journal = International Journal of Urology | volume = 23 | issue = 11 | pages = 946–951 | date = November 2016 | pmid = 27531585 | doi = 10.1111/iju.13172 | doi-access = free }}</ref>
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| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 8.71 || Cardiovascular functioning (agonists increase risk of pulmonary hypertension), empathy (via [[von Economo neurons]]<ref>{{cite web|url=http://neuronbank.org/wiki/index.php/Von_Economo_neuron|title=Von Economo neuron – NeuronBank|website=neuronbank.org}}{{MEDRS|date=October 2017}}</ref>)
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| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 5.02 || Dopamine release into the mesocorticolimbic pathway (agonists ↓); acetylcholine release in the prefrontal cortex (agonists ↑); dopaminergic and noradrenergic activity in the [[frontal cortex]] (antagonists ↑);<ref>{{cite journal | vauthors = Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D | title = The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 3 | pages = 954–964 | date = September 2003 | pmid = 12750432 | doi = 10.1124/jpet.103.051797 | s2cid = 18753440 }}</ref> appetite (agonists ↓); antipsychotic effects (agonists ↑); antidepressant effects (agonists & antagonists ↑)
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| colspan =3 align = center | Other 5-HT receptors
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| [[5-HT3 receptor|5-HT<sub>3</sub>]] || 593 || Emesis (agonists ↑); anxiolysis (antagonists ↑).
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| [[5-HT4 receptor|5-HT<sub>4</sub>]] || 125.89 || Movement of food across the GI tract (agonists ↑); memory & learning (agonists ↑); antidepressant effects (agonists ↑). Signalling via [[Gs alpha subunit|G<sub>αs</sub>]] activation of adenylyl cyclase.
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| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || 251.2 || Memory consolidation.<ref>{{cite journal | vauthors = Gonzalez R, Chávez-Pascacio K, Meneses A | title = Role of 5-HT5A receptors in the consolidation of memory | journal = Behavioural Brain Research | volume = 252 | pages = 246–251 | date = September 2013 | pmid = 23735322 | doi = 10.1016/j.bbr.2013.05.051 | s2cid = 140204585 }}</ref> Signals via [[Gi alpha subunit|G<sub>i/o</sub>]] inhibition of [[adenylyl cyclase]].
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| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 98.41 || Cognition (antagonists ↑); antidepressant effects (agonists & antagonists ↑); [[anxiogenic]] effects (antagonists ↑<ref>{{cite journal | vauthors = Nautiyal KM, Hen R | title = Serotonin receptors in depression: from A to B | journal = F1000Research | volume = 6 | pages = 123 | year = 2017 | pmid = 28232871 | pmc = 5302148 | doi = 10.12688/f1000research.9736.1 | doi-access = free }}</ref>). [[Gs alpha subunit|G<sub>s</sub>]] signalling via activating [[adenylyl cyclase]].
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| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 8.11 || Cognition (antagonists ↑); antidepressant effects (antagonists ↑). Acts by [[Gs alpha subunit|G<sub>s</sub>]] signalling via activating [[adenylyl cyclase]].
|}