PT  - JOURNAL ARTICLE
AU  - Paul A Insel
AU  - Andrea Wilderman
AU  - Alexander Zambon
AU  - Aaron Snead
AU  - Fiona Murray
AU  - Nakon Aroonsakool
AU  - Daniel McDonald
AU  - Shu zhu
AU  - Thalia McCann
AU  - Lingzhi Zhang
AU  - Krishna Sriram
AU  - Amy Chinn
AU  - Alexander V. Michkov
AU  - Rebecca Lynch
AU  - Aaron Overland
AU  - Ross Corriden
TI  - GPCR Expression in Native Cells: "Novel" endoGPCRs as Physiologic Regulators and Therapeutic Targets
AID  - 10.1124/mol.115.098129
DP  - 2015 Mar 03
TA  - Molecular Pharmacology
PG  - mol.115.098129
4099  - http://molpharm.aspetjournals.org/content/early/2015/03/03/mol.115.098129.short
4100  - http://molpharm.aspetjournals.org/content/early/2015/03/03/mol.115.098129.full
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, especially orphan, GPCRs regulate cell function and can be therapeutic targets. Knowledge is limited regarding the GPCRs expressed by native cells that are activated by endogenous ligands (endoGPCRs). Here, we review approaches to define their 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.