PT - JOURNAL ARTICLE AU - Paul A. Insel AU - Andrea Wilderman AU - Alexander C. Zambon AU - Aaron N. Snead AU - Fiona Murray AU - Nakon Aroonsakool AU - Daniel S. McDonald AU - Shu Zhou AU - Thalia McCann AU - Lingzhi Zhang AU - Krishna Sriram AU - Amy M. Chinn AU - Alexander V. Michkov AU - Rebecca M. Lynch AU - Aaron C. Overland AU - Ross Corriden TI - G Protein–Coupled Receptor (GPCR) Expression in Native Cells: “Novel” endoGPCRs as Physiologic Regulators and Therapeutic Targets AID - 10.1124/mol.115.098129 DP - 2015 Jul 01 TA - Molecular Pharmacology PG - 181--187 VI - 88 IP - 1 4099 - http://molpharm.aspetjournals.org/content/88/1/181.short 4100 - http://molpharm.aspetjournals.org/content/88/1/181.full SO - Mol Pharmacol2015 Jul 01; 88 AB - G protein–coupled receptors (GPCRs), the largest family of signaling receptors in the human genome, are also the largest class of targets of approved drugs. Are the optimal GPCRs (in terms of efficacy and safety) currently targeted therapeutically? Especially given the large number (∼120) of orphan GPCRs (which lack known physiologic agonists), it is likely that previously unrecognized GPCRs, especially orphan receptors, regulate cell function and can be therapeutic targets. Knowledge is limited regarding the diversity and identity of GPCRs that are activated by endogenous ligands and that native cells express. Here, we review approaches to define GPCR expression in tissues and cells and results from studies using these approaches. We identify problems with the available data and suggest future ways to identify and validate the physiologic and therapeutic roles of previously unrecognized GPCRs. We propose that a particularly useful approach to identify functionally important GPCRs with therapeutic potential will be to focus on receptors that show selective increases in expression in diseased cells from patients and experimental animals.