RT Journal Article
SR Electronic
T1 The Pharmacology and Function of Short Chain Fatty Acid Receptors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.115.102301
DO 10.1124/mol.115.102301
A1 Daniele Bolognini
A1 Andrew B Tobin
A1 Graeme Milligan
A1 Catherine E Moss
YR 2015
UL http://molpharm.aspetjournals.org/content/early/2015/12/30/mol.115.102301.abstract
AB Despite some block-buster G protein-coupled receptor (GPCR) drugs only a small fraction (~15%) of the more than 390 non-odorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent de-orphanization programmes that have opened the prospect of extending the reach of new medicine design to novel receptor types with potential therapeutic value. Prominent among these receptors are those that respond to short chain free fatty acids of carbon chain length 2-6. These receptors, FFA2 (GPR43) and FFA3 (GPR41), are each predominantly activated by the short chain fatty acids acetate, propionate and butyrate, ligands that originate largely as fermentation by-products of anaerobic bacteria in the gut. However, the presence of FFA2 and FFA3 on pancreatic β-cells, FFA3 on neurons and FFA2 on leukocytes and adipocytes means that the biological role of these receptors likely extends beyond that of the widely accepted role of regulating peptide hormone release from enteroendocrine cells in the gut. Here we review the physiological roles of FFA2 and FFA3, the recent development and use of receptor selective pharmacological tool compounds and genetic models available to study these receptors, and present evidence of the potential therapeutic value of targeting this emerging receptor pair.