Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B

Abstract

GPR109B (HM74) is a putative G protein-coupled receptor (GPCR)whose cognate ligands have yet to be characterized. GPR109B shows a high degree of sequence similarity to GPR109A, another GPCR that was identified as a high-affinity nicotinic acid (niacin) receptor. However, the affinity of nicotinic acid to GPR109B is very low. In this study, we found that certain aromatic D

International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)

“…Consistent with this, HCA 2 and HCA 3 receptors, which are expressed in neutrophils, macrophages, and other immune cells, have been shown to mediate ligand-induced increases in free intracellular Ca 2ϩ concentrations in a G i /G o -dependent manner (Benyó et al, 2006;Tang et al, 2006;Kostylina et al, 2008;Ahmed et al, 2009a;Irukayama-Tomobe et al, 2009). It has been suggested that the increase in intracellular Ca 2ϩ concentrations mediated by HCA 2 receptors in response to nicotinic acid results in the activation of Ca 2ϩ -sensitive phospholipase A 2 and subsequent formation of prostanoids (Benyó et al, 2005(Benyó et al, , 2006Tang et al, 2006).…”

“…The HCA 3 receptor is expressed in adipose tissue (Soga et al, 2003;Tunaru et al, 2003;Wise et al, 2003), and this expression can be increased by activation of PPAR␥ (Jeninga et al, 2009). In addition, the HCA 3 receptor is expressed in various immune cells, including neutrophils, monocytes, and macrophages (Nomura et al, 1993;Yousefi et al, 2000;Ahmed et al, 2009a;Irukayama-Tomobe et al, 2009). Expression in neutrophils has been shown to be stimulated by granulocyte macrophage-colony-stimulating factor (Yousefi et al, 2000), whereas expression in primary human monocytes and phorbol 12-myristate 13-acetate-differentiated THP1 and U937 monocytic cell lines can be increased by hypoxia (Knowles et al, 2006).…”

“…After the identification of the HCA 2 receptor as a nicotinic acid and ketone body receptor and the discovery of ligands activating HCA 1 and HCA 3 receptors, it has been shown in numerous models that the effects mediated by all three receptors are inhibited by pertussis toxin (Soga et al, 2003;Tunaru et al, 2003;Wise et al, 2003;Cai et al, 2008;Ge et al, 2008;Ahmed et al, 2009a;Irukayama-Tomobe et al, 2009;Liu et al, 2009). Thus, HCA 1 , HCA 2 , and HCA 3 receptors are G i /G o -coupled receptors.…”

Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Anti-lipolytic G-protein-coupled Receptor 81 (GPR81/Gpr81)

“…GPR109A has been identified as the receptor for the antilipolytic drug nicotinic acid, and in GPR109A knock-out mice it has been shown that GPR109A was the receptor mediating the lipid-lowering effects of nicotinic acid (34 -36). Recently, the ketone body ␤-hydroxybutyrate was reported as an endogenous agonist for GPR109A (39), whereas aromatic D-amino acids can activate GPR109B (40). In addition, very recently two reports (41,42) showed that GPR81 functions as a receptor for lactate, which reduces lipolysis in vitro and in vivo (43,44).…”

The gene signature in CCAAT-enhancer-binding protein dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors

“…Moreover, several of the C/EBPα signature genes, such as Id1, 26,27 GPR109B, 22 ANXA1, 23 and IL18RAP, 28 have been directly related to granulocyte differentiation or function. Collectively, these results indicate that C/EBPα activation up-regulates the expression of 33 genes, defining a C/EBPα signature, which may be directly implicated in neutrophil differentiation and function.…”