Abstract
Dopamine D2 receptors, similar to other G-protein-coupled receptors, exist in a high- and low-affinity state for agonists. Based upon a review of the methods for detecting D2 receptor agonist high-affinity states, we discuss alterations of such states in animal models of disease and the implications of such alterations for their labelling with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. The classic approach of detecting agonist high-affinity states compares agonist competition for antagonist radioligands, in most cases using [3H]-spiperone as the radioligand; alternative approaches and radioligands have been proposed, but their claimed advantages have not been substantiated by other investigators. In view of the advantages and disadvantages of various techniques, we critically have reviewed reported findings on the detection of D2 receptor agonist high-affinity states in a variety of animal models. These data are compared to the less numerous findings from human in vivo studies based on PET and SPECT tracers; they are interpreted in light of the finding that D2 receptor agonist high-affinity states under control conditions may differ between rodent and human brain. The potential advantages of agonist ligands in studies of pathophysiology and as diagnostics are being discussed.
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Abbreviations
- COMT:
-
Catechol-O-methyl transferase
- D2high :
-
Agonist high-affinity state of the D2 dopamine receptor
- DBH:
-
Dopamine β-hydroxylase
- GPCR:
-
G-protein-coupled receptor
- Gprk6:
-
G-protein-coupled receptor kinase 6
- MNPA:
-
2-Methoxy-N-propylnorapomorphine
- NMSP:
-
N-methylspiperone
- NPA:
-
N-propylnorapomorphine
- PET:
-
Positron emission tomography
- SPECT:
-
Single-photon emission computed tomography
- DAT:
-
Dopamine transporter
- VMAT:
-
Vesicular monoamine transporter
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Acknowledgments
Work in the authors’ lab has been supported by a grant from the Dutch Technology Foundation STW (grant 10127).
Conflict of interest
MCM is an employee of Boehringer Ingelheim, a company marketing the D2 agonist pramipexole.
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van Wieringen, JP., Booij, J., Shalgunov, V. et al. Agonist high- and low-affinity states of dopamine D2 receptors: methods of detection and clinical implications. Naunyn-Schmiedeberg's Arch Pharmacol 386, 135–154 (2013). https://doi.org/10.1007/s00210-012-0817-0
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DOI: https://doi.org/10.1007/s00210-012-0817-0