دانلود رایگان مقاله لاتین امپدانس سیگنالینگ از سایت الزویر
عنوان فارسی مقاله:
تجزیه و تحلیل مبتنی بر امپدانس سیگنالینگ گیرنده مواد مخدر مو و مکانیزم اساسی
عنوان انگلیسی مقاله:
Impedance-based analysis of mu opioid receptor signaling and underlying mechanisms
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
The mu opioid receptor (MOR) is a member of the opioid family of receptors and the large G-protein coupled receptor (GPCR) superfamily. Activation of this receptor results in a GDP/GTP exchange at specific G-proteins with the resulting release of the G-protein subunits leading to stimulation of downstream effector pathways. Receptor activation can also result in the recruitment of β-arrestin leading to receptor internalisation and the activation of a G-protein independent signaling pathway. Agonists can activate different pathway subsets leading to signaling bias [1,2]. The opioid agonists [D-Ala2 , NMe-Phe4 , Gly-ol5 ]-enkephalin (DAMGO) and morphine are both MOR agonists which have been shown to exhibit bias in their signaling [3,4]. One measure of this bias is the induction of receptor internalisation. In the majority of cell types, treatment with DAMGO leads to internalisation while morphine shows relatively less internalisation [5–8]. A second illustration of bias is the observation that in β-arrestin2 knockout mice, morphine analgesia is enhanced while respiratory depression is reduced [9]. In addition to ligand bias changing the level at which pathways can be activated, the outcomes of receptor stimulation can be influenced by type or state of a cell. There is also the possibility of unexpected pathways being activated causing the full set of effects to be missed [3,5,6,10,11]. A system with a read-out capturing the whole cell response to receptor activation will allow a holistic comparison of agonists. Label-free real-time cellular analysis (RTCA) platforms allow an approach naïve to the actual mechanisms activated but instead capture an integrated whole-cell output. This can include cell processes that have not previously been described [11,12]. One RTCA platform uses an impedance based assay, which measures the change in impedance over time produced by cultured cells grown on an array of interdigitated circuits on the base of a 96-well microplate. This provides an output integrating the whole cell signals that lead to a change in impedance resulting from ligand stimulation. The assay is label-free and provides for a real-time analysis of cell events [13,14]. This technique is starting to be utilised to examine GPCR ligands with a goal of allowing an unbiased method of classifying ligands into discrete pharmacological categories and to give an indication of their signaling bias [12,15]. Most of the underlying mechanisms that lead to ligandinduced cellular morphological changes and a change in cellular impedance are not well understood. A better understanding of what cellular processes underlie impedance profiles will allow a more confident assessment of compounds and the prediction of their properties. This may have applications such as the screening of compounds for desirable properties.
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کلمات کلیدی:
AN ANALYSIS OF THE MU OPIOID RECEPTOR AND GPR177 ... https://etda.libraries.psu.edu/catalog/10954 by JJ Jin - 2010 - Related articles Wnt secretion; Wntless; GPR177; mu-opioid receptor; protein-protein interaction ... been identified and shown to affect MOR biogenesis, trafficking, and signaling. ... the underlying mechanisms involved in the development of opioid addiction. Involvement of Mu Opioid Receptor Signaling in the ... - NCBI - NIH https://www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC) by S Eftekhar-Vaghefi - 2015 - Cited by 2 - Related articles However, the exact mechanism(s) underlying such neuroprotection, especially ... The results suggest that μ-opioid receptors signaling participate in the opioid .... The cells were analyzed immediately on the fluorescence plate reader (FLX 800, ... Constitutive Activity in Receptors and Other Proteins https://books.google.com/books?isbn=0123812992 2010 - Science Identification of a novel “almost neutral” mu-opioid receptor antagonist in ... G proteins and opioid receptor-mediated signaling. Cell. Signal. 9, 237–248. ... In vivo pA2 analysis of naltrexone antagonism of discriminative stimulus and ... Constitutive mu opioid receptor activation as a regulatory mechanism underlying narcotic ... Analysis of opioid efficacy, tolerance, addiction and dependence from ... https://www.ncbi.nlm.nih.gov › NCBI › Literature › PubMed Central (PMC) by MM Morgan - 2011 - Cited by 60 - Related articles For example, analysis of the signalling cascade from µ-opioid receptors to voltage ..... A major goal is to determine the mechanisms underlying tolerance so ... Opioid Receptors—Advances in Research and Application: 2013 Edition https://books.google.com/books?isbn=1481690671 2013 - Science mouse mPFC concomitant activation of either delta- or mu-opioid receptors, but not ... Double immunofluorescence analysis of cultured cortical cells indicated that a large ... of mu- and delta-opioid receptors enhances DA Dl-like receptor signaling likely ... The mechanisms underlying its transmission process have not been ... Clinical Pain Management Second Edition: Acute Pain https://books.google.com/books?isbn=1444109790 Pamela Macintyre, David Rowbotham, Suellen Walker - 2008 - Health & Fitness The human delta-opioid receptor: genomic organization, cDNA cloning, functional ... How individual sensitivity to opiates can be predicted by gene analyses. ... underlying individual and interstrain differences in opioid actions: focus on the mu ... mutation in the human mu-opioid receptor severely impairs receptor signaling.
