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==Biological activity== <small>L</small>-Proline has been found to act as a weak [[agonist]] of the [[glycine receptor]] and of both [[NMDA receptor|NMDA]] and non-NMDA ([[AMPA receptor|AMPA]]/[[kainate receptor|kainate]]) [[ionotropic glutamate receptor]]s.<ref name="AcademicPress1995">{{cite book|title=Ion Channel Factsbook: Extracellular Ligand-Gated Channels|url=https://books.google.com/books?id=XqzdupxdZUgC&pg=PA126|date=16 November 1995|publisher=Academic Press|isbn=978-0-08-053519-7|pages=126|url-status=live|archive-url=https://web.archive.org/web/20160426213947/https://books.google.com/books?id=XqzdupxdZUgC&pg=PA126|archive-date=26 April 2016}}</ref><ref name="pmid1349155">{{cite journal | vauthors = Henzi V, Reichling DB, Helm SW, MacDermott AB | title = L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons | journal = Molecular Pharmacology | volume = 41 | issue = 4 | pages = 793–801 | date = April 1992 | doi = 10.1016/S0026-895X(25)09065-0 | pmid = 1349155 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1349155 | archive-url = https://archive.today/20150115015124/http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1349155 | url-status = dead | archive-date = January 15, 2015 }}</ref><ref name="Arslan2014">{{cite book| vauthors = Arslan OE |title=Neuroanatomical Basis of Clinical Neurology | edition = Second |url=https://books.google.com/books?id=UTv6AwAAQBAJ&pg=PA309|date=7 August 2014|publisher=CRC Press|isbn=978-1-4398-4833-3|pages=309|url-status=live|archive-url=https://web.archive.org/web/20160514155908/https://books.google.com/books?id=UTv6AwAAQBAJ&pg=PA309|archive-date=14 May 2016}}</ref> It has been proposed to be a potential [[endogenous]] [[excitotoxin]].<ref name="AcademicPress1995" /><ref name="pmid1349155" /><ref name="Arslan2014" /> In [[plants]], proline accumulation is a common physiological response to various stresses but is also part of the developmental program in [[generative tissues]] (e.g. [[pollen]]).<ref name="pmid18379856">{{cite journal | vauthors = Verbruggen N, Hermans C | title = Proline accumulation in plants: a review | journal = Amino Acids | volume = 35 | issue = 4 | pages = 753–759 | date = November 2008 | pmid = 18379856 | doi = 10.1007/s00726-008-0061-6 | s2cid = 21788988 | url = https://dipot.ulb.ac.be/dspace/bitstream/2013/57922/4/Verbruggen_and_Hermans_2008_Amino_Acids.pdf }}</ref><ref>{{cite journal | vauthors = Shrestha A, Fendel A, Nguyen TH, Adebabay A, Kullik AS, Benndorf J, Leon J, Naz AA | display-authors = 6 | title = Natural diversity uncovers P5CS1 regulation and its role in drought stress tolerance and yield sustainability in barley | journal = Plant, Cell & Environment | pages = 3523–3536 | date = September 2022 | volume = 45 | issue = 12 | pmid = 36130879 | doi = 10.1111/pce.14445 | s2cid = 252438394 | doi-access = free | bibcode = 2022PCEnv..45.3523S }}</ref><ref>{{cite journal | vauthors = Shrestha A, Cudjoe DK, Kamruzzaman M, Siddique S, Fiorani F, Léon J, Naz AA | title = Abscisic acid-responsive element binding transcription factors contribute to proline synthesis and stress adaptation in Arabidopsis | journal = Journal of Plant Physiology | volume = 261 | pages = 153414 | date = June 2021 | pmid = 33895677 | doi = 10.1016/j.jplph.2021.153414 | bibcode = 2021JPPhy.26153414S | s2cid = 233397785 }}</ref><ref>{{cite journal | vauthors = Muzammil S, Shrestha A, Dadshani S, Pillen K, Siddique S, Léon J, Naz AA | title = An Ancestral Allele of ''Pyrroline-5-carboxylate synthase1'' Promotes Proline Accumulation and Drought Adaptation in Cultivated Barley | journal = Plant Physiology | volume = 178 | issue = 2 | pages = 771–782 | date = October 2018 | pmid = 30131422 | pmc = 6181029 | doi = 10.1104/pp.18.00169 }}</ref> A diet rich in proline was linked to an increased risk of depression in humans in a study from 2022 that was tested on a limited pre-clinical trial on humans and primarily in other organisms. Results were significant in the other organisms.<ref name="pmid35508109">{{cite journal | vauthors = Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Martin M, de la Vega-Correa L, Zapata C, Burokas A, Blasco G, Coll C, Escrichs A, Biarnés C, Moreno-Navarrete JM, Puig J, Garre-Olmo J, Ramos R, Pedraza S, Brugada R, Vilanova JC, Serena J, Gich J, Ramió-Torrentà L, Pérez-Brocal V, Moya A, Pamplona R, Sol J, Jové M, Ricart W, Portero-Otin M, Deco G, Maldonado R, Fernández-Real JM | display-authors = 6 | title = Microbiota alterations in proline metabolism impact depression | journal = Cell Metabolism | volume = 34 | issue = 5 | pages = 681–701.e10 | date = May 2022 | pmid = 35508109 | doi = 10.1016/j.cmet.2022.04.001 | s2cid = 248528026 | hdl = 10230/53513 | doi-access = free | hdl-access = free }}</ref>
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