TY - JOUR
T1 - The G protein-coupled receptor, class C, group 6, subtype A (GPRC6A) receptor
T2 - from cloning to physiological function
AU - Clemmensen, C
AU - Smajilovic, S
AU - Wellendorph, P
AU - Bräuner-Osborne, Hans
N1 - This article is protected by copyright. All rights reserved.
PY - 2014
Y1 - 2014
N2 - GPRC6A (G protein-coupled receptor, class C, group 6, subtype A) is a class C G protein-coupled receptor, that has been cloned from human, mouse and rat. Several groups have shown that the receptor is activated by a range of basic and small aliphatic L-α-amino acids of which L-arginine, L-lysine and L-ornithine are the most potent compounds with EC50 values in the mid micromolar range. In addition, several groups have shown that the receptor is either directly activated or positively modulated by divalent cations such as Ca(2+) albeit in concentrations above 5 mM, which is above the physiological concentration in most tissues. More recently, the peptide osteocalcin and the steroid testosterone have also been suggested to be endogenous GPRC6A agonists. The receptor is widely expressed in all three species which, along with the omnipresence of the amino acids and divalent cation ligands, suggest that the receptor could be involved in a broad range of physiological functions. So far, this has mainly been addressed by analyses of genetically modified mice where the GPRC6A receptor has been ablated. Although there has been some discrepancies among results reported from different groups, there is increasing evidence that the receptor is involved in regulation of inflammation, metabolism and endocrine functions. GPRC6A could thus be an interesting target for new drugs in these therapeutic areas.
AB - GPRC6A (G protein-coupled receptor, class C, group 6, subtype A) is a class C G protein-coupled receptor, that has been cloned from human, mouse and rat. Several groups have shown that the receptor is activated by a range of basic and small aliphatic L-α-amino acids of which L-arginine, L-lysine and L-ornithine are the most potent compounds with EC50 values in the mid micromolar range. In addition, several groups have shown that the receptor is either directly activated or positively modulated by divalent cations such as Ca(2+) albeit in concentrations above 5 mM, which is above the physiological concentration in most tissues. More recently, the peptide osteocalcin and the steroid testosterone have also been suggested to be endogenous GPRC6A agonists. The receptor is widely expressed in all three species which, along with the omnipresence of the amino acids and divalent cation ligands, suggest that the receptor could be involved in a broad range of physiological functions. So far, this has mainly been addressed by analyses of genetically modified mice where the GPRC6A receptor has been ablated. Although there has been some discrepancies among results reported from different groups, there is increasing evidence that the receptor is involved in regulation of inflammation, metabolism and endocrine functions. GPRC6A could thus be an interesting target for new drugs in these therapeutic areas.
U2 - 10.1111/bph.12365
DO - 10.1111/bph.12365
M3 - Journal article
C2 - 24032653
SN - 0007-1188
VL - 171
SP - 1129
EP - 1141
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 5
ER -