The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system

Bradley, S. J. , Tobin, A. B. and Prihandoko, R. (2018) The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system. Neuropharmacology, 136(Part C), pp. 421-426. (doi:10.1016/j.neuropharm.2017.11.043) (PMID:29191752)

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Abstract

Chemical genetic has played an important role in linking specific G protein-coupled receptor (GPCR) signalling to cellular processes involved in central nervous system (CNS) functions. Key to this approach has been the modification of receptor properties such that receptors no longer respond to endogenous ligands but rather can be activated selectively by synthetic ligands. Such modified receptors have been called Receptors Activated Solely by Synthetic Ligands (RASSLs) or Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Unlike knock-out animal models which allow detection of phenotypic changes caused by loss of receptor functions, RASSL and DREADD receptors offer the possibility of rescuing "knock-out" phenotypic deficits by administration of the synthetic ligands. Here we describe the use of these modified receptors in defining the physiological role of GPCRs and validation of receptors as drug targets.

Item Type:Articles
Keywords:Central nervous system, chemical genetics, designer receptors activated by designer drugs, muscarinic receptors, receptors activated solely by synthetic ligands.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Prihandoko, Dr Rudi and Tobin, Andrew and Bradley, Dr Sophie
Authors: Bradley, S. J., Tobin, A. B., and Prihandoko, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Neuropharmacology
Publisher:Elsevier
ISSN:0028-3908
ISSN (Online):1873-7064
Published Online:27 November 2017
Copyright Holders:Copyright © 2017 Elsevier Ltd.
First Published:First published in Neuropharmacology 136(Part C):421-426
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
744711GPR120: a G protein-coupled receptor with the potential to regulate insulin secretion and inflammationAndrew TobinBiotechnology and Biological Sciences Research Council (BBSRC)BB/K019856/1RI MOLECULAR CELL & SYSTEMS BIOLOGY