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Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging

The concept of the high‐affinity state postulates that a certain subset of G‐protein‐coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmis...

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Autores principales: Shalgunov, Vladimir, van Waarde, Aren, Booij, Jan, Michel, Martin C., Dierckx, Rudi A. J. O., Elsinga, Philip H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587759/
https://www.ncbi.nlm.nih.gov/pubmed/30450619
http://dx.doi.org/10.1002/med.21552
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author Shalgunov, Vladimir
van Waarde, Aren
Booij, Jan
Michel, Martin C.
Dierckx, Rudi A. J. O.
Elsinga, Philip H.
author_facet Shalgunov, Vladimir
van Waarde, Aren
Booij, Jan
Michel, Martin C.
Dierckx, Rudi A. J. O.
Elsinga, Philip H.
author_sort Shalgunov, Vladimir
collection PubMed
description The concept of the high‐affinity state postulates that a certain subset of G‐protein‐coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high‐affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high‐affinity state with positron emission tomography (PET). This review provides an overview of agonist tracers that have been developed for PET imaging of the brain, and the experimental paradigms that have been developed for the estimation of the relative abundance of receptors configured in the high‐affinity state. Agonist tracers appear to be more sensitive to endogenous neurotransmitter challenge than antagonists, as was originally expected. However, other expectations regarding agonist tracers have not been fulfilled. Potential reasons for difficulties in detecting the high‐affinity state in vivo are discussed.
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spelling pubmed-65877592019-07-02 Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging Shalgunov, Vladimir van Waarde, Aren Booij, Jan Michel, Martin C. Dierckx, Rudi A. J. O. Elsinga, Philip H. Med Res Rev Review Articles The concept of the high‐affinity state postulates that a certain subset of G‐protein‐coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high‐affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high‐affinity state with positron emission tomography (PET). This review provides an overview of agonist tracers that have been developed for PET imaging of the brain, and the experimental paradigms that have been developed for the estimation of the relative abundance of receptors configured in the high‐affinity state. Agonist tracers appear to be more sensitive to endogenous neurotransmitter challenge than antagonists, as was originally expected. However, other expectations regarding agonist tracers have not been fulfilled. Potential reasons for difficulties in detecting the high‐affinity state in vivo are discussed. John Wiley and Sons Inc. 2018-11-18 2019-05 /pmc/articles/PMC6587759/ /pubmed/30450619 http://dx.doi.org/10.1002/med.21552 Text en © 2018 The Authors. Medicinal Research Reviews Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Articles
Shalgunov, Vladimir
van Waarde, Aren
Booij, Jan
Michel, Martin C.
Dierckx, Rudi A. J. O.
Elsinga, Philip H.
Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title_full Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title_fullStr Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title_full_unstemmed Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title_short Hunting for the high‐affinity state of G‐protein‐coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging
title_sort hunting for the high‐affinity state of g‐protein‐coupled receptors with agonist tracers: theoretical and practical considerations for positron emission tomography imaging
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587759/
https://www.ncbi.nlm.nih.gov/pubmed/30450619
http://dx.doi.org/10.1002/med.21552
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