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

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).

SUBMITTER: Schulz S

PROVIDER: S-EPMC514508 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

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

Schulz Stefan S Mayer Dana D Pfeiffer Manuela M Stumm Ralf R Koch Thomas T Höllt Volker V

The EMBO journal 20040722 16

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 ...[more]

PMID: 15272312

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