Inhibition of endothelin A receptor by a novel, selective receptor antagonist enhances morphine-induced analgesia: Possible functional interaction of dimerized endothelin A and μ-opioid receptors

Kuroda, Yui; Nonaka, Miki; Kamikubo, Yuji; Ogawa, Hirotaka; Murayama, Takashi; Kurebayashi, Nagomi; Sakairi, Hakushun; Miyano, Kanako; Komatsu, Akane; Dodo, Tetsushi; Nakano-Ito, Kyoko; Yamaguchi, Kazuya; Sakurai, Takashi; Iseki, Masako; Hayashida, Masakazu; Uezono, Yasuhito

doi:10.1016/j.biopha.2021.111800

Cited by 7 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Muñoz & Rosso 2010, Chan et al 2014, Tricco et al 2016, do Vale et al 2019 but are also routinely used to assess the activation of specific biological pathways by other therapeutic interventions, particularly during drug development (e.g. Schäfer et al 2003, Burghardt et al 2007, Kuroda et al 2021. Receptor antagonists prevent a biological response by binding to and blocking a single receptor type, rather than binding to and activating it like an agonist.…”

Section: Comparisonmentioning

confidence: 99%

How to gain evidence for causation in disease and therapeutic intervention: from Koch’s postulates to counter-counterfactuals

Evans

2022

Med Health Care and Philos

View full text Add to dashboard Cite

Researchers, clinicians, and patients have good reasons for wanting answers to causal questions of disease and therapeutic intervention. This paper uses microbiologist Robert Koch’s pioneering work and famous postulates to extrapolate a logical sequence of evidence for confirming the causes of disease: association between individuals with and without a disease; isolation of causal agents; and the creation of a counterfactual (demonstrating that an agent is sufficient to reproduce the disease anew). This paper formally introduces counter-counterfactuals, which appear to have been used, perhaps intuitively, since the time of Koch and possibly earlier. An argument is presented that counter-counterfactuals (disease-preventers) are a useful tool for identifying necessary causes of disease, and sometimes must be used in place of isolation which is not always possible. In addition, a logical sequence of causal evidence for a therapeutic intervention is presented: creating a counterfactual (demonstrating that the intervention is sufficient to change the natural course of a disease), comparisons between subjects in receipt of treatment versus those who are not (typically within a randomised controlled trial, which can quantify effects of intervention), and counter-counterfactuals (treatment-preventers, which can identify the intervention’s mechanisms of action).

show abstract

Section: Comparisonmentioning

confidence: 99%

How to gain evidence for causation in disease and therapeutic intervention: from Koch’s postulates to counter-counterfactuals

Evans

2022

Med Health Care and Philos

View full text Add to dashboard Cite

show abstract

“…The cADDis cAMP assay system using the cADDis cAMP assay kit (#U0200G) (Montana Molecular, Bozeman, MT, USA) has been described previously [27]. Briefly, cells were seeded at 5.0 × 10 4 cells/well (Halotag ® MOR/pGS22F) on black-walled, clear, flatbottomed 96-well plates with recombinant BacMam virus expressing the cADDis sensor and 0.6 µM sodium butyrate and incubated for 24 h at 5% CO 2 at 37 • C. The medium was replaced with 100 µL of Krebs solution, and the cells were incubated at 28 • C for 30 min in the dark.…”

Section: Caddis Camp Assaymentioning

confidence: 99%

Ketamine Improves Desensitization of µ-Opioid Receptors Induced by Repeated Treatment with Fentanyl but Not with Morphine

et al. 2022

Self Cite

View full text Add to dashboard Cite

The issue of tolerance to continuous or repeated administration of opioids should be addressed. The ability of ketamine to improve opioid tolerance has been reported in clinical studies, and its mechanism of tolerance may involve improved desensitization of μ-opioid receptors (MORs). We measured changes in MOR activity and intracellular signaling induced by repeated fentanyl and morphine administration and investigated the effects of ketamine on these changes with human embryonic kidney 293 cells expressing MOR using the CellKey™, cADDis cyclic adenosine monophosphate, and PathHunter® β-arrestin recruitment assays. Repeated administration of fentanyl or morphine suppressed the second MOR responses. Administration of ketamine before a second application of opioids within clinical concentrations improved acute desensitization and enhanced β-arrestin recruitment elicited by fentanyl but not by morphine. The effects of ketamine on fentanyl were suppressed by co-treatment with an inhibitor of G-protein-coupled receptor kinase (GRK). Ketamine may potentially reduce fentanyl tolerance but not that of morphine through modulation of GRK-mediated pathways, possibly changing the conformational changes of β-arrestin to MOR.

show abstract

“…A new class of genetically encoded, fluorescent biosensors make it possible to image the release, spread, and clearance of important neurotransmitters and modulators in the extracellular space (Marvin et al, 2013 ; Patriarchi et al, 2018 ; Unger et al, 2020 ). In turn the stimulation of the GPCRs and subsequent intracellular signaling pathways can now be studied in real time, capturing the kinetics and spatial distribution of the signaling that the neurotransmitters provoke (Ferrandon et al, 2009 ; Zhao et al, 2011 ; Lohse et al, 2012 ; Vilardaga et al, 2014 ; Irannejad et al, 2015 ; Ohno et al, 2017 ; Greenwald et al, 2018 ; Halls and Canals, 2018 ; Jullie et al, 2020 ; Olsen et al, 2020 ; Kuroda et al, 2021 ; Wright and Bouvier, 2021 ; Zhang et al, 2021b ). We are moving beyond the question of whether signaling has occurred to a new era in which we can watch in real time the exact nature of where and when these important events occur.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Kinetics of Signaling and Arrestin Recruitment by Nervous System G-Protein Coupled Receptors

Hoare

Tewson

Sachdev

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Neurons integrate inputs over different time and space scales. Fast excitatory synapses at boutons (ms and μm), and slow modulation over entire dendritic arbors (seconds and mm) are all ultimately combined to produce behavior. Understanding the timing of signaling events mediated by G-protein-coupled receptors is necessary to elucidate the mechanism of action of therapeutics targeting the nervous system. Measuring signaling kinetics in live cells has been transformed by the adoption of fluorescent biosensors and dyes that convert biological signals into optical signals that are conveniently recorded by microscopic imaging or by fluorescence plate readers. Quantifying the timing of signaling has now become routine with the application of equations in familiar curve fitting software to estimate the rates of signaling from the waveform. Here we describe examples of the application of these methods, including (1) Kinetic analysis of opioid signaling dynamics and partial agonism measured using cAMP and arrestin biosensors; (2) Quantifying the signaling activity of illicit synthetic cannabinoid receptor agonists measured using a fluorescent membrane potential dye; (3) Demonstration of multiplicity of arrestin functions from analysis of biosensor waveforms and quantification of the rates of these processes. These examples show how temporal analysis provides additional dimensions to enhance the understanding of GPCR signaling and therapeutic mechanisms in the nervous system.

show abstract

Inhibition of endothelin A receptor by a novel, selective receptor antagonist enhances morphine-induced analgesia: Possible functional interaction of dimerized endothelin A and μ-opioid receptors

Cited by 7 publications

References 47 publications

How to gain evidence for causation in disease and therapeutic intervention: from Koch’s postulates to counter-counterfactuals

How to gain evidence for causation in disease and therapeutic intervention: from Koch’s postulates to counter-counterfactuals

Ketamine Improves Desensitization of µ-Opioid Receptors Induced by Repeated Treatment with Fentanyl but Not with Morphine

Quantifying the Kinetics of Signaling and Arrestin Recruitment by Nervous System G-Protein Coupled Receptors

Contact Info

Product

Resources

About