Niacin receptor 1

Hydroxycarboxylic acid receptor 2
Identifiers
Symbols	HCAR2; GPR109A; HCA2; HM74a; HM74b; NIACR1; PUMAG; Puma-g
External IDs	OMIM: 609163 MGI: 1933383 HomoloGene: 4391 IUPHAR: GeneCards: HCAR2 Gene
Gene Ontology Molecular function • receptor activity • purinergic nucleotide receptor activity, G-protein coupled • nicotinic acid receptor activity Cellular component • plasma membrane • plasma membrane • plasma membrane • integral to membrane Biological process • neutrophil apoptosis • apoptosis • positive regulation of neutrophil apoptosis • negative regulation of lipid catabolic process • positive regulation of adiponectin secretion Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	338442	80885
Ensembl	ENSG00000182782	ENSMUSG00000045502
UniProt	Q8TDS4	Q0VBA6
RefSeq (mRNA)	NM_177551	NM_030701.3
RefSeq (protein)	NP_808219	NP_109626.1
Location (UCSC)	Chr 12: 123.19 – 123.19 Mb	Chr 5: 124.31 – 124.32 Mb
PubMed search	[1]	[2]

Niacin receptor 1, also known as NIACR1 or GPR109A, is a protein which in humans is encoded by the NIACR1 gene.^[1][2][3][4]

Function

GPR109A is a high affinity receptor for nicotinic acid (niacin)^[3][4] and is a member of the nicotinic acid receptor family of G protein-coupled receptors (the other identified member being GPR109B).

GPR109A is a G_i / G_o protein-coupled receptor with high affinity for nicotinic acid.^[3]

Clinical significance

GPR109A is believed to be 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.^[5] In GPR109A knockout mice, the effects of niacin on both lipids^[6] and flushing^[7] is eliminated. Furthermore in arrestin beta 1 knockout mice, niacin's effect on flushing is greatly reduced while the lipid modifying effects are maintained.^[8]

The precise mechanism of action of niacin therapeutic effects has not been fully elucidated but appears to work in part through activation of GPR109A which reduces the levels of intracellular cAMP thereby inhibiting lipolysis in adipocytes.^[9] In contrast, the flushing effect is due to GPR109A activation of ERK 1/2 MAP kinase^[10] mediated by arrestin beta 1.^[8] Activation of MAP kinase in turn causes release of prostaglandin D2 from Langerhans cells in the skin.^[11]

References

1. ^ Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (June 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878. 
2. ^ "Entrez Gene: GPR109A G protein-coupled receptor 109A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=338442. 
3. ^ ^{a b c} Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB (March 2003). "Molecular identification of high and low affinity receptors for nicotinic acid". The Journal of Biological Chemistry 278 (11): 9869–74. doi:10.1074/jbc.M210695200. PMID 12522134. 
4. ^ ^{a b} Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, Furuichi K (March 2003). "Molecular identification of nicotinic acid receptor". Biochemical and Biophysical Research Communications 303 (1): 364–9. doi:10.1016/S0006-291X(03)00342-5. PMID 12646212. 
5. ^ Pike NB (December 2005). "Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid". The Journal of Clinical Investigation 115 (12): 3400–3. doi:10.1172/JCI27160. PMC 1297267. PMID 16322787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1297267. 
6. ^ Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (March 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. 
7. ^ Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S (December 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1297235. 
8. ^ ^{a b} Walters RW, Shukla AK, Kovacs JJ, Violin JD, Dewire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, Lefkowitz RJ (April 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2673863. 
9. ^ Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH, Wang H, Su EW, Mosior MK, Eacho PI, Cao G (August 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. 
10. ^ Richman JG, Kanemitsu-Parks M, Gaidarov I, Cameron JS, Griffin P, Zheng H, Guerra NC, Cham L, Maciejewski-Lenoir D, Behan DP, Boatman D, Chen R, Skinner P, Ornelas P, Waters MG, Wright SD, Semple G, Connolly DT (June 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. 
11. ^ Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, Demarest KT (June 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. 

External links

• "Nicotinic Acid Receptor Family: GPR109A". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3010.