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Can cloned receptors aid drug research?

Published online by Cambridge University Press:  05 December 2011

Paul R. Hartig
Paul R. Hartig
Affiliation:
Synaptic Pharmaceuticals, 215 College Road, Paramus, N.J. 07652, U.S.A.
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Synopsis:

Over 50 different neurotransmitter and hormone receptors have been cloned, transfected and characterised. Within the pharmaceutical industry, the thrust of this research is now moving from receptor cloning to focussed application of these new tools to the task of drug development. With human receptor clones now available, it is possible to target drug design to single human proteins from the inception of a drug-design project. A critical question is whether human genes will express a human pharmacology when expressed in non-human, non-neuronal cell lines. Relevant results from studies with the human serotonin 5-HT2 and 5-HT1D receptors are presented, including the cloning of a rat 5-HT1B receptor which is homologous to a human 5-HT1D receptor gene. Another issue is the relationship between agonist and antagonist binding sites. The ability to study individual human receptors in selected cell lines which are free from interfering receptors has helped to advance our understanding of this relationship. Studies comparing agonist and antagonist binding sites of the human 5-HT2 receptor are described. Finally, the fact that so many neurotransmitter receptors belong to the same gene superfamily, the G-protein-coupled or 7TM (7 transmembrane domain) receptor superfamily, allows us to form new insights about receptor structure and function. Examples where comparative studies of gene sequences are helping to predict pharmacological properties of drugs are described.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 99 , Issue 1-2: The Advancement of Drug Discovery , 1992 , pp. 19 - 25
Copyright
Copyright © Royal Society of Edinburgh 1992

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