Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

A Gillis, AB Gondin, A Kliewer, J Sanchez, HD Lim… - Science …, 2020 - science.org
Biased agonism at G protein–coupled receptors describes the phenomenon whereby some
drugs can activate some downstream signaling activities to the relative exclusion of others. …

[HTML][HTML] Critical assessment of G protein-biased agonism at the μ-opioid receptor

A Gillis, A Kliewer, E Kelly, G Henderson… - Trends in …, 2020 - cell.com
G protein-biased agonists of the μ-opioid receptor (MOPr) have been proposed as an improved
class of opioid analgesics. Recent studies have been unable to reproduce the original …

Emerging paradigms of G protein-coupled receptor dephosphorylation

A Kliewer, RK Reinscheid, S Schulz - Trends in pharmacological sciences, 2017 - cell.com
Elucidation of the molecular mechanisms underlying G protein-coupled receptor (GPCR)
dephosphorylation remains a major challenge. While specific GPCR phosphatases (GRPs) …

[HTML][HTML] Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions

…, K Sviatkó, AR Brás, JC Mariani, A Kliewer… - Journal of Experimental …, 2022 - rupress.org
Disclosures: D. Máthé reported grants from European Union H2020 HCEMM-739593 and
from NRDIO, Hungary, TKP-BIOImaging-2020-4.1. 1-TKP2020 during the conduct of the study. …

Morphine‐induced respiratory depression is independent of β‐arrestin2 signalling

A Kliewer, A Gillis, R Hill, F Schmiedel… - British journal of …, 2020 - Wiley Online Library
Background and Purpose GPCRs can signal through both G proteins and β‐arrestin2. For
the μ‐opioid receptor, early experimental evidence from a single study suggested that G …

Targeting multiple opioid receptors–improved analgesics with reduced side effects?

…, A Mann, E Miess, A Kliewer… - British journal of …, 2018 - Wiley Online Library
Classical opioid analgesics, including morphine, mediate all of their desired and undesired
effects by specific activation of the μ‐opioid receptor (μ receptor). The use of morphine for …

Whole-brain 3D activation and functional connectivity mapping in mice using transcranial functional ultrasound imaging

…, S Cazzanelli, J Ferrier, JC Mariani, A Kliewer… - JoVE (Journal of …, 2021 - jove.com
Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity
measure of the cerebral blood volume achieved by ultrafast doppler angiography…

[HTML][HTML] CXCL14 is no direct modulator of CXCR4

M Otte, A Kliewer, D Schütz, C Reimann, S Schulz… - FEBS letters, 2014 - Elsevier
CXC motif chemokine 12/CXC chemokine receptor type 4 (CXCL12/CXCR4) signaling is
involved in ontogenesis, hematopoiesis, immune function and cancer. Recently, the orphan …

[HTML][HTML] Epigenetic-like stimulation of receptor expression in SSTR2 transfected HEK293 cells as a new therapeutic strategy

…, A Naumann, R Runge, L Huebinger, A Kliewer… - Cancers, 2022 - mdpi.com
Simple Summary Neuroendocrine tumors (NETs) expressing the somatostatin receptor subtype
2 (SSTR2) are promising targets for peptide receptor radionuclide therapy (PRRT) using …

[HTML][HTML] A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening

…, HM Maric, M Spetea, A Kliewer… - Communications …, 2022 - nature.com
Abstract Analysis of agonist-driven phosphorylation of G protein-coupled receptors (GPCRs)
can provide valuable insights into the receptor activation state and ligand pharmacology. …