NOP Receptor Signaling Cascades

2019 ◽  
pp. 131-139 ◽  
Author(s):  
Kyle E. Parker ◽  
Michael R. Bruchas
Keyword(s):  
Signaling Cascades ◽  
Receptor Signaling ◽  
Nop Receptor

scholarly journals Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling

2011 ◽  
Vol 301 (5) ◽  
pp. H1754-H1764 ◽  
Author(s):  
George Vaniotis ◽  
Bruce G. Allen ◽  
Terence E. Hébert
Keyword(s):  
Subcellular Localization ◽  
G Protein ◽  
G Proteins ◽  
Adrenergic Receptor ◽  
Physiological State ◽  
Signaling Cascades ◽  
Special Focus ◽  
The Novel ◽  
Receptor Signaling ◽  
G Protein Coupled

In recent years, we have come to appreciate the complexity of G protein-coupled receptor signaling in general and β-adrenergic receptor (β-AR) signaling in particular. Starting originally from three β-AR subtypes expressed in cardiomyocytes with relatively simple, linear signaling cascades, it is now clear that there are large receptor-based networks which provide a rich and diverse set of responses depending on their complement of signaling partners and the physiological state. More recently, it has become clear that subcellular localization of these signaling complexes also enriches the diversity of phenotypic outcomes. Here, we review our understanding of the signaling repertoire controlled by nuclear β-AR subtypes as well our understanding of the novel roles for G proteins themselves in the nucleus, with a special focus, where possible, on their effects in cardiomyocytes. Finally, we discuss the potential pathological implications of alterations in nuclear β-AR signaling.

Modulation of the NOP receptor signaling affects resilience to acute stress

2019 ◽  
Vol 33 (12) ◽  
pp. 1540-1549 ◽  
Author(s):  
Victor A D Holanda ◽  
Salvatore Pacifico ◽  
Joaquim Azevedo Neto ◽  
Luca Finetti ◽  
Bruno Lobão-Soares ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Stress ◽  
Behavioral Effects ◽  
Emotional States ◽  
Receptor Signaling ◽  
Nop Receptor ◽  
Orphanin Fq ◽  
Receptor System ◽  
Electric Footshock ◽  
First Time

Background: The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are implicated in the modulation of emotional states. Previous human and rodent findings support NOP antagonists as antidepressants. However, the role played by the N/OFQ–NOP receptor system in resilience to stress is unclear. Aims: The present study investigated the effects of activation or blockade of NOP receptor signaling before exposure to acute stress. Methods: The behavioral effects of the administration before stress of the NOP agonists Ro 65-6570 (0.01–1 mg/kg) and MCOPPB (0.1–10 mg/kg), and the NOP antagonist SB-612111 (1–10 mg/kg) were assessed in mice exposed to inescapable electric footshock and forced swim as stressors. The behavioral phenotype of mice lacking the NOP receptor (NOP(-/-)) exposed to inescapable electric footshock was also investigated. Results: The activation of NOP receptor signaling with the agonists increased the percentage of mice developing helpless behavior and facilitated immobile posture. In contrast, the blockade of NOP receptor reduced the acquisition of depressive-like phenotypes, and similar resistance to develop helpless behaviors was observed in NOP(-/-) mice. Under the same stressful conditions, the antidepressant nortriptyline (20 mg/kg) did not change the acquisition of helpless behavior and immobile posture. Conclusions: These findings support the view that NOP activation during acute stress facilitates the development of depressive-related behaviors, whereas NOP blockade has a protective outcome. This study showed for first time that NOP antagonists are worthy of investigation as preemptive treatments in patients with severe risk factors for depression.

scholarly journals Lipid peroxidation and pathological disruption of the ApoE/Reelin-ApoER2-DAB1 axis in sporadic Alzheimer's disease

2021 ◽  
Author(s):  
Christopher E Ramsden ◽  
Gregory S Keyes ◽  
Elizabeth Calzada ◽  
Mark S Horowitz ◽  
Jahandar Jahanipour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Signaling Cascades ◽  
Braak Stage ◽  
Receptor Signaling ◽  
Sporadic Alzheimer’S Disease ◽  
Lim Kinase ◽  
Apoe Receptor ◽  
Apoe Receptors

The strong genetic link between Apolipoprotein E (ApoE) and sporadic Alzheimer's disease (AD) and the marked increase in brain lipid peroxidation observed in early AD suggest that dysfunctional lipid metabolism plays a central role in AD pathogenesis. However, specific mechanisms and targets linking ApoE and lipid peroxidation to AD are not well-defined. Here we used a combination of biochemical experiments, single-marker immunohistochemistry (IHC), and multiplex-IHC to examine the hypothesis that synaptic ApoE receptors and their ligands ApoE and Reelin are susceptible to lipid peroxidation, and that downstream disruptions in ApoE delivery and Reelin-ApoE receptor signaling cascades contribute to the pathogenesis of sporadic AD. We found that (1) Lys and His-enriched sequences within the binding regions of ApoER2, ApoE, VLDLR and Reelin, and recombinant ApoER2, ApoE and Reelin proteins, are vulnerable to attack by aldehydic products of lipid peroxidation, generating lipid-protein adducts and acid-stable ApoE receptor-ligand complexes; (2) ApoER2, lipid peroxidation-modified ApoE, native ApoE, Reelin, and multiple downstream components of Reelin-ApoE receptor signaling cascades that govern synaptic integrity [including DAB1, Tyr232-phosphorylated DAB1, Tyr607-phosphorylated Phosphatidylinositol 3-kinase, Thr508-phosphorylated LIM kinase-1, Ser202/Thr205-phosphorylated Tau and Thr19-phosphorylated-PSD95] accumulate in the immediate vicinity of neuritic plaques and surrounding abnormal neurons, and (3) several of these ApoE/Reelin-ApoE receptor-DAB1 pathway markers positively correlate with Braak stage, Aβ plaque load, and antemortem cognitive impairment. ApoE/Reelin-ApoER2-DAB1 axis pathologies were especially prominent in the dendritic compartments of the molecular layer of the dentate gyrus, cornu ammonis and subiculum, regions that receive synaptic input from the entorhinal-hippocampal projections that underlie memory formation. Taken together, these observations point toward extensive derangements in the ApoE/Reelin-ApoE receptor-DAB1 axis and provide evidence supporting a new, working hypothesis wherein lipid peroxidation-induced adduction and crosslinking of ApoE receptors and ApoE are proximate molecular events that compromise synaptic integrity and contribute to the histopathological hallmarks and cognitive deficits that characterize sporadic AD in humans.

scholarly journals Dishevelled coordinates phosphoinositide kinases PI4KIIIα and PIP5KIγ for efficient PtdInsP2 synthesis

2022 ◽  
Author(s):  
Lizbeth de la Cruz ◽  
Raul Riquelme ◽  
Oscar Vivas ◽  
Andres Barria ◽  
Jill B. Jensen
Keyword(s):  
Plasma Membrane ◽  
Synergistic Effect ◽  
Receptor Activation ◽  
Scaffolding Protein ◽  
Signaling Cascades ◽  
Receptor Signaling ◽  
Cellular Processes ◽  
Lipid Kinases

Phosphatidylinositol(4,5)-bisphosphate (PtdInsP2) is an important modulator of many cellular processes and its abundance in the plasma membrane is closely regulated. We examined the hypothesis that the scaffolding protein Dishevelled can bind the lipid kinases PI4K and PIP5K, facilitating synthesis of PtdInsP2 directly from PtdIns. This report used several assays for PtdInsP2 to examine the cooperative function of phosphoinositide kinases and Dishevelled in the context of two receptor signaling cascades. Simultaneous overexpression of PI4KIIIα and PIP5KIγ had a synergistic effect on PtdInsP2 synthesis that was recapitulated by overexpression of Dishevelled. Increasing the activity of Dishevelled by overexpression increased resting plasma membrane PtdInsP2. Knockdown of Dishevelled reduced resting plasma membrane PtdInsP2 and slowed PtdInsP2 resynthesis following receptor activation. We confirm that Dishevelled promotes coupling of PI4KIIIα and PIP5KIγ and show that this interaction is essential for efficient resynthesis of PtdInsP2 following receptor activation.

scholarly journals Non‐linear interaction between α1‐noradrenergic and P2 receptor signaling cascades in XII motoneurons (MNs)

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Matthew Frank Ireland ◽  
Refik Kanjhan ◽  
A Jung ◽  
Jacqueline Mewes ◽  
Tadafumi Adachi ◽  
...  
Keyword(s):  
Signaling Cascades ◽  
Receptor Signaling ◽  
P2 Receptor ◽  
Linear Interaction ◽  
Non Linear
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