The effects of species ortholog and SNP variation on receptors for free fatty acids

Hudson, B.D. , Murdoch, H. and Milligan, G. (2013) The effects of species ortholog and SNP variation on receptors for free fatty acids. Molecular Endocrinology, 27(8), pp. 1177-1187. (doi: 10.1210/me.2013-1085)

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Although it is widely assumed that species orthologs of hormone responsive G protein-coupled receptors will be activated by the same endogenously produced ligand(s), variation in potency, particularly in cases where more than one receptor responds to the same hormone, can result in challenges in defining the contribution of individual receptors in different species. This can create considerably greater issues when using synthetic chemical ligands and, in some cases, may result in a complete lack of efficacy of such a ligand when used in animal models of pathophysiology. In man, the concept that distinct responses of individuals to medicines may reflect differences in the ability of such drugs to bind to or activate single nucleotide polymorphism variants of receptors is more established as a concept but, in many cases, clear links between such variants that are associated with disease phenotypes and substantial differences in receptor ligand pharmacology have been more difficult to obtain. Herein, we consider each of these issues for the group of receptors, FFA1-FFA4, defined to be activated by free fatty acids of varying chain length which, based on their production by one tissue or location and action in distinct locations, have been suggested to possess characteristics of ‘hormones’.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Hudson, Dr Brian and Murdoch, Dr Hannah and Milligan, Professor Graeme
Authors: Hudson, B.D., Murdoch, H., and Milligan, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular Endocrinology
Publisher:The Endocrine Society
ISSN (Online):1944-9917
Copyright Holders:Copyright © 2013 The Endocrine Society
First Published:First published in Molecular Endocrinology 27(8):1177-1187
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
519861Developing selective ligands for Free Fatty Acid Receptor 2 with novel pharmacological propertiesGraeme MilliganWellcome Trust (WELLCOME)089600/Z/09/ZRI NEUROSCIENCE & PSYCHOLOGY