کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5816063 | 1115552 | 2009 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the μ-opioid receptor
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Recent evidence suggests that opioid analgesia and tolerance can be modulated by metabotropic glutamate receptors. Therefore, we studied the functional coupling and desensitization of the μ-opioid receptor (MOR) in human embryonic kidney (HEK) 293 cells which co-express metabotropic glutamate receptor 5 (mGluR5). As demonstrated by the D-Ala2,N-MePhe4,Gl-ol5-enkephalin (DAMGO)-induced inhibition of intracellular cAMP level and by binding studies, the co-expression of mGluR5 had no substantial effect on the agonist binding sites and functional coupling of the MOR. However, in MOR/mGluR5 co-expressing cells, the non-competitive mGluR5 antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine) decreases the DAMGO-induced MOR phosphorylation, internalization, and desensitization, whereas non-selective competitive mGluR antagonists or agonists had no effects. These findings indicate that an allosteric modulation of mGluR5 can affect the agonist-induced MOR signalling and regulation. As a mechanistic basis for the observed effects we suggested an interaction/heterodimerization of MOR and mGluR5, which is supported by the DAMGO-induced co-internalization of MOR and mGluR5 and by the increase of MPEP binding sites (Bmax) and a change of the binding affinity (KD) of mGluR5 receptors after the co-expression of MOR. In addition, co-immunoprecipitation experiments revealed evidence for an interaction between MOR and mGluR5 which is facilitated by MPEP treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 56, Issue 4, March 2009, Pages 768-778
Journal: Neuropharmacology - Volume 56, Issue 4, March 2009, Pages 768-778
نویسندگان
H. Schröder, D.-F. Wu, A. Seifert, M. Rankovic, S. Schulz, V. Höllt, T. Koch,