Niacin receptor 1
|Hydroxycarboxylic acid receptor 2|
|Symbols||; GPR109A; HCA2; HM74a; HM74b; NIACR1; PUMAG; Puma-g|
|External IDs||IUPHAR: ChEMBL: GeneCards:|
GPR109A is a high-affinity receptor for nicotinic acid (niacin), and is a member of the nicotinic acid receptor family of G protein-coupled receptors (the other identified member being Niacin receptor 2, also known as GPR109B).
Niacin receptor 1 is an important biomolecular target of niacin which is a widely prescribed drug for the treatment of dyslipidemia and to increase HDL cholesterol but whose therapeutic use is limited by flushing. In NIACR1 knockout mice, the effects of niacin on both lipids and flushing is eliminated. Furthermore, in arrestin beta 1 knockout mice, niacin's effect on flushing is greatly reduced while the lipid modifying effects are maintained.
The precise mechanism of action of niacin therapeutic effects has not been fully elucidated, but appears to work in part through activation of NIACR1 which reduces the levels of intracellular cAMP thereby inhibiting lipolysis in adipocytes. In contrast, the flushing effect is due to NIACR1 activation of ERK 1/2 MAP kinase mediated by arrestin beta 1. Activation of MAP kinase in turn causes release of prostaglandin D2 from Langerhans cells in the skin.
The mouse ortholog of NIACR1, Niacr1, has recently been proposed to mediate the ability of 5-oxo-ETE, a member of the 5-HETE family of eicosanoids, to stimulate the production of steroidogenic acute regulatory protein mRNA, Steroidogenic acute regulatory protein, and thereby progesterone in mouse cultured MA-10 Leydig cells. Human tissues respond to 5-oxo-ETE and other 5-HETE family members though the OXER1 G protein-coupled receptor. The roles, if any, of Niacr1 in the response of leydig cells to other 5-HETE family members, of Niacr1 in the response of other mouse cells to 5-HETE family members, and the role of NIACR1 in the response of human tissues to 5-HETE family members has not been determined.
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- "Entrez Gene: GPR109A G protein-coupled receptor 109A".
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- Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K et al. (Mar 2003). "PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect". Nature Medicine 9 (3): 352–5. doi:10.1038/nm824. PMID 12563315.
- Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM et al. (Dec 2005). "GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing". The Journal of Clinical Investigation 115 (12): 3634–40. doi:10.1172/JCI23626. PMC 1297235. PMID 16322797.
- Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM et al. (May 2009). "beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice". The Journal of Clinical Investigation 119 (5): 1312–1321. doi:10.1172/JCI36806. PMC 2673863. PMID 19349687.
- Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH et al. (Aug 2005). "Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A". Biochemical and Biophysical Research Communications 334 (2): 729–32. doi:10.1016/j.bbrc.2005.06.141. PMID 16018973.
- Richman JG, Kanemitsu-Parks M, Gaidarov I, Cameron JS, Griffin P, Zheng H et al. (Jun 2007). "Nicotinic acid receptor agonists differentially activate downstream effectors". The Journal of Biological Chemistry 282 (25): 18028–36. doi:10.1074/jbc.M701866200. PMID 17452318.
- Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, Demarest KT (Jun 2006). "Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A". Biochemical and Biophysical Research Communications 345 (1): 29–37. doi:10.1016/j.bbrc.2006.04.051. PMID 16674924.
- Cooke M, Di Cónsoli H, Maloberti P, Cornejo Maciel F (2013). "Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells". Mol. Cell. Endocrinol. 371 (1-2): 71–8. doi:10.1016/j.mce.2012.11.003. PMID 23159987.
- "Nicotinic Acid Receptor Family: GPR109A". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
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