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

  • Anthony P. Davenport
  • Rhoda E. Kuc
Part of the Methods in Molecular Biology™ book series (MIMB, volume 306)


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, 2, 3, 4, 5, 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


Human peptide

Orphan receptor

Ligand source


Nociceptin/Orphanin FQ


Porcine brain




Bovine stomach


Orexin A and B (hypercretin 1+2)

Orexin 1 and 2

Rat brain


Prolactin Releasing Peptide (PRrP)


Bovine hypothalamus


Ghrelin (motilin related peptide)


Rat stomach


Melanin concentrating hormone (MCH)


Rat whole brain




Peptide library


Tuberoinfundibular peptide 39 (TIP39)


Bovine hypothalamus




Peptide library


Neuromedin U-25 (NMU25)

FM3 and FM4

Peptide library


Neuropeptides FF and AF


Bovine brain


Metastin (Kisspeptin-54)


Human placenta




Peptide library


Urocortin II and I (stresscopins)


Peptide library



LGR7 and LGR8

Peptide library


Bovine adrenomedullary peptide 22 (BAM-22)


Peptide library


Neuropeptides B and W

GPR7 and GPR8

Peptide library


QRFP43 (P52)


Genome database




Porcine brain

See refs. 2 and 3 for further information and citations to original papers.


Autoradiographical Image Unlabeled Ligand Saturation Assay Ligand Program Incubation Tray 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Anthony P. Davenport
    • 1
  • Rhoda E. Kuc
    • 1
  1. 1.Clinical Pharmacology UnitUniversity of Cambridge, Centre for Clinical Investigation, Addenbrooke’s HospitalCambridgeUK

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