Common ligands of G‐protein‐coupled receptors and arginine‐utilizing enzymes

A new family of G‐protein‐coupled receptors (GPRC6A) has recently been described and characterized with unknown physiological role. Three isoforms of GPRC6A are expressed from the same gene by alternative splicing. Agonists for GPRC6A are basic amino acids, particularly the analogues and derivatives of L ‐arginine and L ‐ornithine. These compounds are known ligands of nitric oxide synthase and arginase isoenzymes, but amino‐acid sequences of these enzymes have not shown significant homologies. Various hypotheses for physiological roles of these receptors have been proposed but not yet substantiated. In order to define the most potent agonists, and elucidate further the biological significance of the receptor family, a detailed ligand‐based quantitative structure–activity relationship study may be helpful. British Journal of Pharmacology (2006) 147 , 835–837. doi: 10.1038/sj.bjp.0706683