A glance at G-protein-coupled receptors for lipid mediators: a growing receptor family with remarkably diverse ligands

Pharmacology & Therapeutics
Evi Kostenis

Abstract

A plethora of lipid-like molecules known to act as intracellular second messengers are now recognized to signal cells through plasma membrane 7 transmembrane G-protein-coupled receptors (GPCRs). This has been the result of a decade-long genetic hunt for novel sequences encoding 7 transmembrane receptor proteins and the efforts to pair novel sequences with biologically active substances of (partly) unknown molecular mechanism of action. Identification of novel GPCR ligand pairs represents the first step to shed more light into the mode of action of novel cellular signaling molecules in human health and disease and might represent a fruitful source for the development of new drugs, judged on the successful history of GPCR as drug targets. Since 2000, more than 16 reports became available on lipid mediators--as diverse as lysophospholipids, arachidonic acid metabolites, short-, medium-, and long-chain fatty acids as well as steroid-like molecules--exerting their effects as extracellular mediators via rhodopsin-like family GPCRs. These reports have opened new avenues for research in human lipid receptor physiology and pharmacology. Here, the current knowledge on the recently deorphanized lipid receptors, including their isolation, ...Continue Reading

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