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Ligand-receptor interactions of native and expressed neurotransmitter receptors

Reference	BBS/E/B/51001074
Principal Investigator / Supervisor	Professor David Sattelle
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	189,915
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1999
Duration	30 months

Abstract

Neurotransmitter receptors mediate the actions of primary signalling molecules (neurotransmitters) and are targets of neuroactive drugs and pesticides. Molecular genetics, cloning and site-directed mutagenesis, together with functional expression studies (electrophysiology, calcium imaging) are combined to characterise ligand-receptor interactions and to identify subunits, domains and amino acid residues involved in ligand binding, signal transduction and drug/chemical actions. Work on ionotropic receptors (for acetylcholine) and G-protein coupled receptors (for acetylcholine, 5- HT) is in progress. Multidisciplinarity: This project integrates genetics, molecular biology and physiology in the analysis of neurotransmitter receptor function. This project is relevant to the H&LS and ANRE Foresight and the specific priorities of Drug Creation and Delivery (and CPD Biomolecular Design) and Integrative Biology Technology. The likely benefits of this research are an enhanced understanding of receptor function, in particular, ligand-receptor interactions, ion channel gating and receptor desensitisation. Molecular pharmacology studies will assist in determining the modes of action of endectocide drugs for improvements in animal health (AF Biological Responses to Stress), and will contribute to the design of novel, safer insect control agents (AF, Agriculture in the Environment).Alternative splice variants of a Drosophila GABA receptor have been shown to vary in their affinity for the neurotransmitter. This appears to reflect a novel mechanism of generating functional diversity. The molecular pharmacology of these variants is under investigation. Newly developed D. melanogaster cell lines stably expressing cloned D. melanogaster neurotransmitter receptors provide new tools for research in the Agrochemical Industry that enable high throughput screening of novel compounds. Cell lines containing wild-type and resistant forms of the D. melanogaster GABA receptor offer a laboratory-based test to predict the early onset of field resistance to GABAergic insecticides with applications for Industry. Studies on the mechanism of action of Imidacloprid on native and recombinant Drosophila nicotinic receptors are in progress.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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