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

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journal contribution
posted on 05.04.2019, 07:52 by SJ Bradley, AB Tobin, R Prihandoko
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. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.

Funding

Work described herein was supported by Biotechnology and Biological Sciences Research Council [grant BB/K019856/1] and Medical Research Council Industry Collaboration Agreement (174202/1).

History

Citation

Neuropharmacology, 2018, 136 (Pt C), pp. 421-426

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

AM (Accepted Manuscript)

Published in

Neuropharmacology

Publisher

Elsevier

eissn

1873-7064

Acceptance date

26/11/2017

Copyright date

2017

Available date

05/04/2019

Publisher version

https://www.sciencedirect.com/science/article/pii/S0028390817305816?via=ihub

Language

en