Overview: The nicotinic acid family of receptors (ENSFM00500000271913) respond to organic acids, including the lipid-lowering agents nicotinic acid (niacin), acipimox and acifran (Soga et al., 2003; Tunaru et al., 2003; Wise et al., 2003). Although GPR109A and GPR109B are over 95% homologous at the protein level, the former is activated by submicromolar concentrations of nicotinic acid, while the latter is only activated at millimolar concentrations (Wise et al., 2003), while GPR81 fails to respond to nicotinic acid (Tunaru et al., 2003).
| Nomenclature | GPR109A | GPR109B | GPR81 |
| Other names | Niacin receptor 1, HM74A, Nic1, Puma-G, | Low-affinity nicotinic acid receptor, HM74, Nic2 | GPR104 |
| Ensembl ID | ENSG00000182782 | ENSG00000182442 | ENSG00000196917 |
| Principal transduction | Gi/o (Soga et al., 2003); Tunaru et al., 2003; Wise et al., 2003) | Gi/o (Soga et al., 2003; Wise et al., 2003) | Gi/o (Ge et al., 2008) |
| Selective agonists | Nicotinic acid (Soga et al., 2003; Tunaru et al., 2003; Wise et al., 2003), acipimox (Wise et al., 2003), 3-hydroxybutyrate (Taggart et al., 2005) | 3-Hydroxyoctanoic acid (Ahmed et al., 2009), IBC293 (Semple et al., 2006) | Lactate (Cai et al., 2008; Liu et al., 2009) |
| Probes | [3H]-Nicotinic acid (Soga et al., 2003) | – | – |
Further closely related 7TM receptors include the 5-oxoeicosanoid receptor (ENSG00000162881) and GPR31 (ENSG00000120436).
Glossary
Abbreviation:
- IBC293
1-(1-methylethyl)-1H-benzotriazole-5-carboxylic acid
Further Reading
Boatman PD, Richman JG, Semple G (2008). Nicotinic acid receptor agonists. J Med Chem51: 7653–7662.
Gille A, Bodor ET, Ahmed K, Offermanns S (2008). Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol48: 79–106.
Guyton JR (2007). Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. Curr Opin Lipidol18: 415–420.
Offermanns S (2006). The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends Pharmacol Sci27: 384–390.
Soudijn W, van Wijngaarden I, IJzerman AP (2007). Nicotinic acid receptor subtypes and their ligands. Med Res Rev27: 417–433.
Vosper H (2009). Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia. Br J Pharmacol158: 429–441.
References
- Ahmed K, et al. J Biol Chem. 2009;284:21928–21933. doi: 10.1074/jbc.M109.019455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cai TQ, et al. Biochem Biophys Res Commun. 2008;377:987–991. doi: 10.1016/j.bbrc.2008.10.088. [DOI] [PubMed] [Google Scholar]
- Ge H, et al. J Lipid Res. 2008;49:797–803. doi: 10.1194/jlr.M700513-JLR200. [DOI] [PubMed] [Google Scholar]
- Liu C, et al. J Biol Chem. 2009;284:2811–2822. doi: 10.1074/jbc.M806409200. [DOI] [PubMed] [Google Scholar]
- Semple G, et al. J Med Chem. 2006;49:1227–1230. doi: 10.1021/jm051099t. [DOI] [PubMed] [Google Scholar]
- Soga T, et al. Biochem Biophys Res Commun. 2003;303:364–369. doi: 10.1016/s0006-291x(03)00342-5. [DOI] [PubMed] [Google Scholar]
- Taggart AK, et al. J Biol Chem. 2005;280:26649–26652. doi: 10.1074/jbc.C500213200. [DOI] [PubMed] [Google Scholar]
- Tunaru S, et al. Nat Med. 2003;9:352–355. doi: 10.1038/nm824. [DOI] [PubMed] [Google Scholar]
- Wise A, et al. J Biol Chem. 2003;278:9869–9874. doi: 10.1074/jbc.M210695200. [DOI] [PubMed] [Google Scholar]