The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation.

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Research Abstract Details 

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The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Abstract Text:

M Petraschka,S Li,T L Gilbert,R E Westenbroek,M R Bruchas,S Schreiber,J Lowe,M J Low,J E Pintar,C Chavkin,

Phosphorylation of specific sites in the second intracellular loop and in the C-terminal domain have previously been suggested to cause desensitization and internalization of the mu-opioid receptor (MOP-R). To assess sites of MOP-R phosphorylation in vivo, affinity-purified, phosphoselective antibodies were raised against either phosphothreonine-180 in the second intracellular loop (MOR-P1) or the C-terminal domain of MOP-R containing phosphothreonine-370 and phosphoserine-375 (MOR-P2). We found that MOR-P2-immunoreactivity (IR) was significantly increased within the striatum of wild-type C57BL/6 mice after injection of the agonist fentanyl. Pretreatment with the antagonist naloxone blocked the fentanyl-induced increase. Furthermore, mutant mice lacking MOP-R showed only non-specific nuclear MOR-P2-IR before or after fentanyl treatment, confirming the specificity of the MOR-P2 antibodies. To assess whether MOP-R phosphorylation occurs following endogenous opioid release, we induced chronic neuropathic pain by partial sciatic nerve ligation (pSNL), which caused a significant increase in MOR-P2-IR in the striatum. pSNL also induced signs of mu opioid receptor tolerance demonstrated by a rightward shift in the morphine dose response in the tail withdrawal assay and by a reduction in morphine conditioned place preference (CPP). Mutant mice selectively lacking all forms of the beta-endorphin peptides derived from the proopiomelanocortin (Pomc) gene did not show increased MOR-P2-IR, decreased morphine antinociception, or reduced morphine CPP following pSNL. In contrast gene deletion of either proenkephalin or prodynorphin opioids did not block the effects of pSNL. These results suggest that neuropathic pain caused by pSNL in wild-type mice activates the release of the endogenous opioid beta-endorphin, which subsequently induces MOP-R phosphorylation and opiate tolerance.

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Publishing Authors By Initials

M Petraschka,S Li,TL Gilbert,RE Westenbroek,MR Bruchas,S Schreiber,J Lowe,MJ Low,JE Pintar,C Chavkin,

For similar hormones, hormone substitutes, and hormone antagonists: hormones: peptide hormones: hypothalamic hormones: pro-opiomelanocortin: beta-endorphin research abstracts see: hormones, hormone substitutes, and hormone antagonists: hormones: peptide hormones: hypothalamic hormones: pro-opiomelanocortin: beta-endorphin research

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The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuroscience

VOLUME: 146

Page Numbers: 1795-807

Journal Abbreviation: Neuroscience

ISSN: 0306-4522

DAY: 30

MONTH: 04

YEAR: 2007

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Information

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LANGUAGE: eng

NlmUniqueID: 7605074

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Keywords Mesh Terms:

KEYWORDS: beta-Endorphin

MESH TERMS: metabolism

Chemical & Substance for Abstract: The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation. Information

Substance Name: beta-Endorphin

Registry Number: 60617-12-1

Grant and Affiliation Information for The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation.

AFFILIATION: Department of Pharmacology, University of Washington School of Medicine, Box 357280, 1959 Pacific Avenue Northeast, Seattle, WA 98195-7280, USA.

Country: United States

AGENCY: United States NIDA

GRANT: R01-DA11676

ACRONYM: DA

MEDLINETA: Neuroscience

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