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Receptor Binding Techniques pp 93–120Cite as

Radioligand-Binding and Molecular-Imaging Techniques for the Quantitative Analysis of Established and Emerging Orphan Receptor Systems

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 306))

Abstract

Radioligand binding is widely used to characterize receptors and to determine their anatomical distribution, particularly the superfamily of rhodopsinlike, seven-transmembrane-spanning G protein-coupled receptors (GPCRs). More than 200 receptors that transduce many important physiological processes and are the target for about 50% of all drugs have been identified in this family (1–6) . A further approx 160 or so ″orphan″ GPCRs have been predicted to exist from the human genome and have mRNA sequences characteristic of 7TM GPCRs, but their endogenous ligands await identification. Most of these receptors have been artificially expressed in cell lines linked to a reporter sys- tem to identify when a ligand binds to the receptor (see Chapter 2). This ″re- verse pharmacology″ approach continues to be used to screen compounds from existing or new combinatorial libraries of biologically active molecules, and has been very successful. More than 45 receptors have been ″de-orphanized″ or paired with their cognate ligand, with nearly half of these putative endo- genous transmitters turning out to be peptides (see Table 1). The number of pairings continues to increase. It is estimated that about 70 of the remaining orphan receptors could turn out to have a peptidic ligand (3).

Table 1 Orphan Receptors Recently Paired With Their Cognate Peptidic Ligands
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Authors and Affiliations

  1. Clinical Pharmacology Unit, University of Cambridge, Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, UK

    Anthony P. Davenport & Rhoda E. Kuc

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  1. Anthony P. Davenport
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Editors and Affiliations

  1. Clinical Pharmacology Unit, University of Cambridge, Centre for Clinical Investigation, Addenbrooke7s Hospital, Cambridge, UK

    Anthony P. Davenport

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Davenport, A.P., Kuc, R.E. (2005). Radioligand-Binding and Molecular-Imaging Techniques for the Quantitative Analysis of Established and Emerging Orphan Receptor Systems. In: Davenport, A.P. (eds) Receptor Binding Techniques. Methods in Molecular Biology™, vol 306. Humana Press. https://doi.org/10.1385/1-59259-927-3:093

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  • DOI: https://doi.org/10.1385/1-59259-927-3:093

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-420-3

  • Online ISBN: 978-1-59259-927-1

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