Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors

Jan Peter van Wieringen (Corresponding author), Martin C. Michel, Henk M. Janssen, Anton G. Janssen, Philip H. Elsinga, Jan Booij

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)

    Abstract

    Background: Dopamine D2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists are more sensitive to detect dopamine release than antagonist radiopharmaceuticals, but this theory has been challenged. Interestingly, not all agonists similarly activate the classic cyclic adenosine mono phosphate (cAMP) and the β-arrestin-2 pathway, some stimulate preferentially one of these pathways; a phenomenon called biased agonism. Because these pathways can be affected separately by pathologies or drugs (including dopamine releasers), it is important to know how agonist radiotracers act on these pathways. Therefore, we characterized the intracellular signalling of the well-known D2/3R agonist radiopharmaceuticals NPA and PHNO and of several novel D2/3R agonists. Methods: cAMP accumulation and β-arrestin-2 recruitment were measured on cells expressing human D2R. Results: All tested agonists showed (almost) full agonism in both pathways. Conclusions: The tested D2/3R agonist radiopharmaceuticals did not exhibit biased agonism in vitro. Consequently, it is likely that drugs (including psychostimulants like amphetamines) and/or pathologies that influence the cAMP and/or the β-arrestin-2 pathway may influence the binding of these radiopharmaceuticals.

    Original languageEnglish
    Article number53
    Number of pages6
    JournalPsychonomic Bulletin and Review
    Volume4
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 1997

    Fingerprint

    Dopamine D2 Receptors
    Radiopharmaceuticals
    Adenine Nucleotides
    Amphetamines
    Dopamine
    Pathology
    Dopamine Agents
    Dopamine Antagonists
    Imaging
    Pathway
    Pharmaceutical Preparations
    beta-Arrestin 1
    Phosphate
    Agonism

    Keywords

    • Dopamine D receptor
    • Intracellular signalling
    • PET/SPECT

    Cite this

    van Wieringen, Jan Peter ; Michel, Martin C. ; Janssen, Henk M. ; Janssen, Anton G. ; Elsinga, Philip H. ; Booij, Jan. / Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors. In: Psychonomic Bulletin and Review. 1997 ; Vol. 4, No. 1.
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    abstract = "Background: Dopamine D2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists are more sensitive to detect dopamine release than antagonist radiopharmaceuticals, but this theory has been challenged. Interestingly, not all agonists similarly activate the classic cyclic adenosine mono phosphate (cAMP) and the β-arrestin-2 pathway, some stimulate preferentially one of these pathways; a phenomenon called biased agonism. Because these pathways can be affected separately by pathologies or drugs (including dopamine releasers), it is important to know how agonist radiotracers act on these pathways. Therefore, we characterized the intracellular signalling of the well-known D2/3R agonist radiopharmaceuticals NPA and PHNO and of several novel D2/3R agonists. Methods: cAMP accumulation and β-arrestin-2 recruitment were measured on cells expressing human D2R. Results: All tested agonists showed (almost) full agonism in both pathways. Conclusions: The tested D2/3R agonist radiopharmaceuticals did not exhibit biased agonism in vitro. Consequently, it is likely that drugs (including psychostimulants like amphetamines) and/or pathologies that influence the cAMP and/or the β-arrestin-2 pathway may influence the binding of these radiopharmaceuticals.",
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    Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors. / van Wieringen, Jan Peter (Corresponding author); Michel, Martin C.; Janssen, Henk M.; Janssen, Anton G.; Elsinga, Philip H.; Booij, Jan.

    In: Psychonomic Bulletin and Review, Vol. 4, No. 1, 53, 01.01.1997.

    Research output: Contribution to journalArticleAcademicpeer-review

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    AU - Michel, Martin C.

    AU - Janssen, Henk M.

    AU - Janssen, Anton G.

    AU - Elsinga, Philip H.

    AU - Booij, Jan

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