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The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides

Author

Listed:
  • Max Meyrath

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29)

  • Martyna Szpakowska

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29)

  • Julian Zeiner

    (University of Bonn, Nussallee 6)

  • Laurent Massotte

    (University of Liège, avenue de l’hopital)

  • Myriam P. Merz

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29)

  • Tobias Benkel

    (University of Bonn, Nussallee 6
    University of Bonn)

  • Katharina Simon

    (University of Bonn, Nussallee 6)

  • Jochen Ohnmacht

    (University of Luxembourg, avenue du Swing 6
    University of Luxembourg, avenue du Swing 6)

  • Jonathan D. Turner

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29)

  • Rejko Krüger

    (University of Luxembourg, avenue du Swing 6
    Luxembourg Institute of Health (LIH), rue Thomas Edison 1A-B)

  • Vincent Seutin

    (University of Liège, avenue de l’hopital)

  • Markus Ollert

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29
    University of Southern Denmark)

  • Evi Kostenis

    (University of Bonn, Nussallee 6)

  • Andy Chevigné

    (Luxembourg Institute of Health (LIH), rue Henri Koch 29)

Abstract

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7, hitherto known as an atypical scavenger receptor for chemokines, is a broad-spectrum scavenger of opioid peptides. Phylogenetically, ACKR3 is intermediate between chemokine and opioid receptors and is present in various brain regions together with classical opioid receptors. Functionally, ACKR3 is a scavenger receptor for a wide variety of opioid peptides, especially enkephalins and dynorphins, reducing their availability for the classical opioid receptors. ACKR3 is not modulated by prescription opioids, but we show that an ACKR3-selective subnanomolar competitor peptide, LIH383, can restrain ACKR3’s negative regulatory function on opioid peptides in rat brain and potentiate their activity towards classical receptors, which may open alternative therapeutic avenues for opioid-related disorders. Altogether, our results reveal that ACKR3 is an atypical opioid receptor with cross-family ligand selectivity.

Suggested Citation

  • Max Meyrath & Martyna Szpakowska & Julian Zeiner & Laurent Massotte & Myriam P. Merz & Tobias Benkel & Katharina Simon & Jochen Ohnmacht & Jonathan D. Turner & Rejko Krüger & Vincent Seutin & Markus O, 2020. "The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16664-0
    DOI: 10.1038/s41467-020-16664-0
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    Cited by:

    1. Evi Kostenis & Jesus Gomeza & Elke Miess-Tanneberg & Nina Kathleen Blum & Tobias Benkel & Andy Chevigné & Carsten Hoffmann & Peter Kolb & Viacheslav Nikolaev & Maria Waldhoer & Martyna Szpakowska & As, 2023. "Reply to: How carvedilol does not activate β2-adrenoceptors," Nature Communications, Nature, vol. 14(1), pages 1-3, December.
    2. Tobias Benkel & Mirjam Zimmermann & Julian Zeiner & Sergi Bravo & Nicole Merten & Victor Jun Yu Lim & Edda Sofie Fabienne Matthees & Julia Drube & Elke Miess-Tanneberg & Daniela Malan & Martyna Szpako, 2022. "How Carvedilol activates β2-adrenoceptors," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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