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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Meyrath M,Szpakowska M,Zeiner J,Massotte L,Merz MP,Benkel T,Simon K,Ohnmacht J,Turner JD,Krüger R,Seutin V,Ollert M,Kostenis E,Chevigné A

doi

10.1038/s41467-020-16664-0

subject

Has Abstract

pub_date

2020-06-19 00:00:00

pages

3033

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16664-0

journal_volume

11

pub_type

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