TY - JOUR T1 - International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B) JF - Pharmacological Reviews JO - Pharmacol Rev SP - 269 LP - 290 DO - 10.1124/pr.110.003301 VL - 63 IS - 2 AU - Stefan Offermanns AU - Steven L. Colletti AU - Timothy W. Lovenberg AU - Graeme Semple AU - Alan Wise AU - Adriaan P. IJzerman Y1 - 2011/06/01 UR - http://pharmrev.aspetjournals.org/content/63/2/269.abstract N2 - The G-protein-coupled receptors GPR81, GPR109A, and GPR109B share significant sequence homology and form a small group of receptors, each of which is encoded by clustered genes. In recent years, endogenous ligands for all three receptors have been described. These endogenous ligands have in common that they are hydroxy-carboxylic acid metabolites, and we therefore have proposed that this receptor family be named hydroxy-carboxylic acid (HCA) receptors. The HCA1 receptor (GPR81) is activated by 2-hydroxy-propanoic acid (lactate), the HCA2 receptor (GPR109A) is a receptor for the ketone body 3-hydroxy-butyric acid, and the HCA3 receptor (GPR109B) is activated by the β-oxidation intermediate 3-hydroxy-octanoic acid. HCA1 and HCA2 receptors are found in most mammalian species, whereas the HCA3 receptor is present only in higher primates. The three receptors have in common that they are expressed in adipocytes and are coupled to Gi-type G-proteins mediating antilipolytic effects in fat cells. HCA2 and HCA3 receptors are also expressed in a variety of immune cells. HCA2 is a receptor for the antidyslipidemic drug nicotinic acid (niacin) and related compounds, and there is an increasing number of synthetic ligands mainly targeted at HCA2 and HCA3 receptors. The aim of this article is to give an overview on the discovery and pharmacological characterization of HCAs, and to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature. We will also discuss open questions regarding this receptor family as well as their physiological role and therapeutic potential. ER -