Nuclear G-protein-coupled receptors as putative novel pharmacological targets

Cell surface G-protein-coupled receptors (GPCRs) are targets for ∼ 30% of drugs currently on the market, and are the largest group of gene products targeted by drugs. Until recently, signaling mediated by GPCRs was thought to emanate exclusively from the cell membrane as a response to extracellular stimuli. However, recent research has revealed the existence of nuclear (n)GPCRs with the ability to trigger identical and/or distinct signaling pathways to their respective counterparts on the cell surface. Understanding of the GPCR signaling platform on the nuclear membranes and its involvement in physiology and/or pathophysiology will be important to develop selective pharmacological and pharmaceutical approaches. In this review, we summarize our current understanding of nGPCRs, with emphasis on their potential as novel pharmacological targets.