China
Africa
Explore chapters and articles related to this topic
The Role of Platelet-Activating Factor in the Pathogenesis of Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
PAF binds to a unique and specific G-protein–coupled PAF receptor typically found in lipid rafts and activates a series of downstream events (5). Studies have utilized cell culture analyses, animal models, and biochemical modeling to demonstrate that following PAF activation, there is phosphorylation and up-regulation of several second messengers, including protein kinase, tyrosine kinase (6), beta arrestin (7), protein kinase B (AkT), mitogen activated protein kinase, and extracellular signal-related kinase (ERK), with activation of the caspase/apoptosis pathway (8), release of NF-kB inhibition (9), and with activation of transcription factor pathways leading to the production and release of inflammatory mediators, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, nitric oxide, and many others. In addition, PAF has been shown to activate the expression of human toll-like receptor 4 (TLR4) (10), and this molecule has been shown to play a critical role in the pathophysiology of necrotizing enterocolitis (NEC) (11).
Experimental perturbations to investigate cardiovascular physiology
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
When studying receptor agonists, ideally a full dose- response curve should be carried out, but this is often limited by the viability of experimental preparations over time. If a single dose or a few doses only are to be used, it is important to do preliminary experiments to establish that these are appropriate and not subthreshold or supramaximal. Also, when designing experimental protocols with agonists, it should be remembered that continual stimulation can lead to desensitization and eventually internalization of the receptors. An example of this is with the β adrenergic receptor, which after continued stimulation, becomes phos- phorylated by a beta-adrenergic receptor kinase 1 (beta- ARK-1) or G-protein coupled receptor kinase 2. Binding of beta-arrestin-1 then leads to desensitization of the receptor and its internalization via endocytosis. The activity of beta- arrestin-1 and beta-ARK-1 are influenced by the levels of cyclic adenosine monophosphate, the second messenger of the β adrenergic receptor itself.
Functional GLP-1R antibodies identified from a synthetic GPCR-focused library demonstrate potent blood glucose control
Published in mAbs, 2021
Qiang Liu, Pankaj Garg, Burcu Hasdemir, Linya Wang, Emily Tuscano, Emily Sever, Erica Keane, Ana G Lujan Hernandez, Tom Z. Yuan, Eric Kwan, Joyce Lai, Greg Szot, Sreenivasan Paruthiyil, Fumiko Axelrod, Aaron K. Sato
When a GPCR is activated by an agonist, β-arrestins are recruited to the GPCR from the cytosol, thereby excluding the receptor from further G protein interactions and leading to signal arrest, hence the name “arrestin”.35 To determine if TB01-3 had any effects on β-arrestin recruitment by activated GLP-1 R, GLP-1 R-over-expressing CHO-K1 cells (DiscoverX) that are specifically designed and validated for assessing GLP-1 R β-arrestin recruitment were used in the following manner. Cells were pre-incubated with a 3-fold titration of TB01-3 from 100 nM down for 1 hr at room temperature (RT) to allow binding to occur and then stimulated with 10 nM GLP-1 7–36. TB01-3 demonstrated inhibition of GLP-1 7–36 peptide-induced beta arrestin recruitment to GLP-1 R in a dose-response curve for β-arrestin recruitment (Figure 8c). This indicated that TB01-3 reduces β-arrestin recruitment to GLP-1 R, which is consistent with the observed reduced receptor activation. Thus, these cell-based assays indicate that TB01-3 is an antagonist to GLP-1 7–36 for GLP-1 R.
Investigational opioid antagonists for treating opioid-induced bowel dysfunction
Published in Expert Opinion on Investigational Drugs, 2018
Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi
Unlike the analgesic effect, tolerance was not observed for constipation. In order to explain the underlying mechanism of OIBD, different segments of GI tract were examined. The regulation of mu-opioid receptors varies between the GI segments. This mechanism is due to difference of signals associated with beta-arrestin-2 in central and enteric neurons. Beta-arrestin-2 is an intracellular protein known to have a role in tolerance to analgesic effect of opioids. It has been suggested that different role of β-arrestin2 should be considered in development of new investigations with less adverse effects [46]. There are investigations on a new mu-opioid receptor agonist to induce a different pathway. TRV130 is suggested to have bias for G-protein signaling other than beta-arrestin pathway. The findings have shown that this pathway does not decrease OIC [47].
Roles of M3 receptor in the effect of penehyclidine hydrochloride upregulated beta-arrestin-1 expression in LPS-stimulated HPMVEC
Published in Journal of Receptors and Signal Transduction, 2019
Liu Qs, Chen K, Liu Ap, Xiao F, He Qw, Li Z, Yuan Qh, Wang Yl, Zhang Zz, Zhan J
Beta-arrestins play key roles in the regulation of multiple G protein-coupled receptors (GPCRs)-dependent and -independent signaling pathways [14,15]. Beta-arrestins bind to the activated and phosphorylated state of these receptors, consequently blocking the ability of the receptors to activate G protein [16,17]. This beta-arrestin-mediated regulation of transcription appears to play an important role in cell growth, apoptosis and modulation of immune functions [18]. In our study, compared to LPS groups, a dramatic increase in beta-arrestin-1 expression was detected after exposure of cells to PHC. These data suggest that the protective effects of PHC on pulmonary microvascular endothelial barrier integrity may exert through upregulation of beta-arrestin-1.