Hydroxycarboxylic acid receptor 1

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config |display-authors=6 |name-list-style=vanc}} {{Infobox gene}} '''Hydroxycarboxylic acid receptor 1''' ('''HCA1'''), formerly known as '''G protein-coupled receptor 81''' ('''GPR81'''), is a protein that in humans is encoded by the ''HCAR1'' gene.<ref name="entrez">{{cite web |title=Entrez Gene: GPR81 G protein-coupled receptor 81 |url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=27198}}</ref><ref name="pmid11574155">{{cite journal |vauthors=Lee DK, Nguyen T, Lynch KR, Cheng R, Vanti WB, Arkhitko O, Lewis T, Evans JF, George SR, O'Dowd BF |date=September 2001 |title=Discovery and mapping of ten novel G protein-coupled receptor genes |journal=Gene |volume=275 |issue=1 |pages=83–91 |doi=10.1016/S0378-1119(01)00651-5 |pmid=11574155}}</ref> HCA1, like the other hydroxycarboxylic acid receptors HCA2 and HCA3, is a {{nowrap|Gi/o-coupled}} G protein-coupled receptor (GPCR).<ref name="IUPHAR's comprehensive 2011 review on HCARs" /><ref name="IUPHAR-DB HCAR family page" /> The primary endogenous agonist of HCA1 is lactic acid (and its conjugate base, lactate).<ref name="IUPHAR's comprehensive 2011 review on HCARs">{{cite journal |vauthors=Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP |date=June 2011 |title=International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B) |journal=Pharmacological Reviews |volume=63 |issue=2 |pages=269–90 |doi=10.1124/pr.110.003301 |pmid=21454438 |doi-access=free}}</ref><ref name="IUPHAR-DB HCAR family page">{{cite web |title=Hydroxycarboxylic acid receptors |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=48 |access-date=13 July 2018 |website=IUPHAR/BPS Guide to Pharmacology |publisher=International Union of Basic and Clinical Pharmacology |vauthors=Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG}}</ref> More recently, 3,5-dihydroxybenzoic acid has been reported to activate HCA1.<ref name="pmid37096487">{{cite journal |vauthors=Wagner W, Sobierajska K, Pułaski Ł, Stasiak A, Ciszewski WM |date=April 2023 |title=Whole grain metabolite 3,5-dihydroxybenzoic acid is a beneficial nutritional molecule with the feature of a double-edged sword in human health: a critical review and dietary considerations |journal=Critical Reviews in Food Science and Nutrition |volume=64 |issue=24 |pages=8786–8804 |doi=10.1080/10408398.2023.2203762 |pmid=37096487 |s2cid=258310985}}</ref>

Lactate was initially found to activate HCA1 on fat cells and thereby to inhibit these cells lipolysis i.e., break-down of their fats into free fatty acids and glycerol.<ref name="pmid19047060">{{cite journal |vauthors=Liu C, Wu J, Zhu J, Kuei C, Yu J, Shelton J, Sutton SW, Li X, Yun SJ, Mirzadegan T, Mazur C, Kamme F, Lovenberg TW |date=January 2009 |title=Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81 |journal=The Journal of Biological Chemistry |volume=284 |issue=5 |pages=2811–22 |doi=10.1074/jbc.M806409200 |pmid=19047060 |doi-access=free}}</ref><ref name="pmid18952058">{{cite journal |vauthors=Cai TQ, Ren N, Jin L, Cheng K, Kash S, Chen R, Wright SD, Taggart AK, Waters MG |date=December 2008 |title=Role of GPR81 in lactate-mediated reduction of adipose lipolysis |journal=Biochemical and Biophysical Research Communications |volume=377 |issue=3 |pages=987–91 |doi=10.1016/j.bbrc.2008.10.088 |pmid=18952058 |bibcode=2008BBRC..377..987C }}</ref> Subsequent studies have found that in addition to fat cells, HCA1 is expressed on cells in the brain, skeletal muscle, lymphoid tissue, uterus, kidney, liver, and pancreas as well as on immune cells such as macrophages and antigen-presenting cells. In the brain, HCA1 acts to dampen neuron excitation and may also function to promote neurogenesis (the production of neurons from neural stem cells) and angiogenesis (the formation of new blood vessels from pre-existing blood vessels). The functions of HCA1 in non-fat and non-neural tissues have not been fully defined but in many cases appear to involve promoting the survival of cells, including various types of cancer cells.<ref name="pmid37391123">{{cite journal |vauthors=Colucci AC, Tassinari ID, Loss ED, de Fraga LS |date=June 2023 |title=History and Function of the Lactate Receptor GPR81/HCAR1 in the Brain: A Putative Therapeutic Target for the Treatment of Cerebral Ischemia |journal=Neuroscience |volume=526 |pages=144–163 |doi=10.1016/j.neuroscience.2023.06.022 |pmid=37391123 |s2cid=259279124}}</ref>

==Ligands== ;Agonists * AZ'5538<ref>{{cite journal |vauthors=Jones NK, Stewart K, Czopek A, Menzies RI, Thomson A, Moran CM, Cairns C, Conway BR, Denby L, Livingstone DE, Wiseman J, Hadoke PW, Webb DJ, Dhaun N, Dear JW, Mullins JJ, Bailey MA |date=May 2020 |title=Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation |journal=Hypertension |volume=75 |issue=5 |pages=1213–1222 |doi=10.1161/HYPERTENSIONAHA.119.14308 |pmc=7176350 |pmid=32200679}}</ref>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal |vauthors=Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S |date=June 2002 |title=Identification of G protein-coupled receptor genes from the human genome sequence |journal=FEBS Letters |volume=520 |issue=1–3 |pages=97–101 |doi=10.1016/S0014-5793(02)02775-8 |pmid=12044878 |bibcode=2002FEBSL.520...97T |s2cid=7116392 |doi-access=free}} * {{cite journal |vauthors=Mao M, Biery MC, Kobayashi SV, Ward T, Schimmack G, Burchard J, Schelter JM, Dai H, He YD, Linsley PS |date=June 2004 |title=T lymphocyte activation gene identification by coregulated expression on DNA microarrays |journal=Genomics |volume=83 |issue=6 |pages=989–99 |doi=10.1016/j.ygeno.2003.12.019 |pmid=15177553}} * {{cite journal |vauthors=Madaan A, Nadeau-Vallée M, Rivera JC, Obari D, Hou X, Sierra EM, Girard S, Olson DM, Chemtob S |date=September 2016 |title=Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1) |journal=American Journal of Obstetrics and Gynecology |volume=216 |issue=1 |pages=60.e1–60.e17 |doi=10.1016/j.ajog.2016.09.072 |pmid=27615440 |doi-access=free}} {{refend}}

Category:G protein-coupled receptors