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 Communjournal_title
Nature communicationsauthors
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 Adoi
10.1038/s41467-020-16664-0subject
Has Abstractpub_date
2020-06-19 00:00:00pages
3033issue
1issn
2041-1723pii
10.1038/s41467-020-16664-0journal_volume
11pub_type
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