| Description: |
The hydroxycarboxylic acid receptors []are members of the rhodopsin-like G protein-coupled receptor (GPCR) family. There are three hydroxycarboxylic acid receptors, termed HCAR1-3. The family was formerly known as nicotinic acid receptor family, although nicotinic acid only shows submicromolar potency at HCAR2 [, ].The receptors respond to organic acids, including the endogenous short chain fatty acids, butyric acid and L-lactic acid, as well as the lipid lowering agents nicotinic acid (niacin), acipimox and acifran [, , ]. There is an increasing number of synthetic ligands mainly targeted at HCAR2 and HCAR3 receptors [, ]. All three receptors are expressed in adipocytes, and are coupled to Gi type G-proteins mediating antilipolytic effects in fat cells [, , , ]. HCAR2 and HCAR3 are also expressed in a variety of immune cells including monocytes, macrophages, neutrophils and Langerhans cells [, ]. HCAR1 and HCAR2 are found in most mammalian species, whereas HCAR3 is only present in higher primates []. There is evidence that these receptors can mediate anti-inflammatory effects. HCAR2 has been shown to be a receptor for the anti-dyslipidemic drug nicotinic acid (niacin) as well as for the anti-psoriatic drug monomethyl-fumarate [, ]. This entry represents two members of hydroxycarboxylic acid receptor family, hydroxycarboxylic acid receptor 2 (also known as niacin receptor 1, G protein-coupled receptor 109A, nicotinic acid receptor, HM74A) and hydroxycarboxylic acid receptor 3 (also known as niacin receptor 2, G protein-coupled receptor 109B, low affinity nicotinic acid receptor). The endogenous ligands of HCAR2 and HCAR3 are beta-D-hydroxybutyric acid and 3-hydroxyoctanoic acid, respectively []. |
