ArticlePloS one2009
Naloxone's pentapeptide binding site on filamin A blocks Mu opioid receptor-Gs coupling and CREB activation of acute morphine.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 62 citations in OpenAlex.
- Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to Alter Persistent Pain: A Randomized, Double-blind, Controlled Study.The Clinical journal of pain · 2015Trial
- Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.Psychopharmacology · 2010Trial
- Low-Dose Naltrexone: What is the Evidence? A Narrative Review.Advances in therapy · 2026Review
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- Toll-Like Receptor 4 Signaling and Drug Addiction.Frontiers in pharmacology · 2020Review
- Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization.Medical sciences (Basel, Switzerland) · 2018Review
- Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation.IBRO reports · 2016Article
- Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats.British journal of pharmacology · 2016Article
- Pharmacological characterization of the opioid inactive isomers (+)-naltrexone and (+)-naloxone as antagonists of toll-like receptor 4.British journal of pharmacology · 2016Article
- Actin filament reorganization in astrocyte networks is a key functional step in neuroinflammation resulting in persistent pain: novel findings on network restoration.Neurochemical research · 2015Article
- Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4.CNS & neurological disorders drug targets · 2015Review
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- Spatio-temporal profiling of Filamin A RNA-editing reveals ADAR preferences and high editing levels outside neuronal tissues.RNA biology · 2013Article
- Complex roles of filamin-A mediated cytoskeleton network in cancer progression.Cell & bioscience · 2013Article
- Naloxone inhibits immune cell function by suppressing superoxide production through a direct interaction with gp91phox subunit of NADPH oxidase.Journal of neuroinflammation · 2012Article
- Ser/ Thr residues at α3/β5 loop of Gαs are important in morphine-induced adenylyl cyclase sensitization but not mitogen-activated protein kinase phosphorylation.The FEBS journal · 2012Article
Corrections and comments
- Retraction · 2022-03-30Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Manipulation of Images · · see also: https://pubpeer.com/publications/FFE5E8F7E73D0ECA931EEF424B9E70
- Retracted
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic morphine causes the mu opioid receptor (MOR) to switch its coupling from Gi/o to Gs, resulting in excitatory signaling via both Galphas and its Gbetagamma dimer. Ultra-low-dose naloxone (NLX) prevents this switch and attenuates opioid tolerance and dependence. This protective effect is mediated via a high-affinity interaction of NLX to a pentapeptide region in c-terminal filamin A (FLNA), a scaffolding protein interacting with MOR. In organotypic striatal slice cultures, we now show that acute morphine induces a dose-dependent Go-to-Gs coupling switch at 5 and 15 min that resolves by 1 hr. The acute Gs coupling induced by 100 microM morphine was completely prevented by co-treatment with 100 pM NLX, (+)NLX, or naltrexone (NTX), or their pentapeptide binding site (FLNA(2561-2565)), which we show can act as a decoy for MOR or bind to FLNA itself. All of these co-treatments presumably prevent the MOR-FLNA interaction. Since ultra-low-dose NTX also attenuates the addictive properties of opioids, we assessed striatal cAMP production and CREB phosphorylation at S(133). Correlating with the Gs coupling, acute morphine induced elevated cAMP levels and a several-fold increase in pS(133)CREB that were also completely blocked by NLX, NTX or the FLNA pentapeptide. We propose that acute, robust stimulation of MOR causes an interaction with FLNA that allows an initially transient MOR-Gs coupling, which recovers with receptor recycling but persists when MOR stimulation is repeated or prolonged. The complete prevention of this acute, morphine-induced MOR-Gs coupling by 100 pM NLX/NTX or 10 microM pentapeptide segment of FLNA further elucidates both MOR signaling and the mechanism of action of ultra-low-dose NLX or NTX in attenuating opioid tolerance, dependence and addictive potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.