Format

Send to

Choose Destination
See comment in PubMed Commons below
EMBO J. 2004 Aug 18;23(16):3282-9. Epub 2004 Jul 22.

Morphine induces terminal micro-opioid receptor desensitization by sustained phosphorylation of serine-375.

Author information

1
Institut für Pharmakologie und Toxikologie, Otto-von-Guericke-Universität, Magdeburg, Germany. stefan.schulz@medizin.uni-magdeburg.de

Abstract

Morphine is a poor inducer of micro-opioid receptor (MOR) internalization, but a potent inducer of cellular tolerance. Here we show that, in contrast to full agonists such as [D-Ala(2)-MePhe(4)-Gly-ol]enkephalin (DAMGO), morphine stimulated a selective phosphorylation of the carboxy-terminal residue 375 (Ser(375)). Ser(375) phosphorylation was sufficient and required for morphine-induced desensitization of MOR. In the presence of full agonists, morphine revealed partial agonistic properties and potently inhibited MOR phosphorylation and internalization. Upon removal of the drug, DAMGO-desensitized receptors were rapidly dephosphorylated. In contrast, morphine-desensitized receptors remained at the plasma membrane in a Ser(375)-phosphorylated state for prolonged periods. Thus, morphine promotes terminal MOR desensitization by inducing a persistent modification of Ser(375).

PMID:
15272312
PMCID:
PMC514508
DOI:
10.1038/sj.emboj.7600334
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center