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Non-Peptide Opioids...
Non-Peptide Opioids Differ in Effects on Mu-Opioid (MOP) and Serotonin 1A (5-HT1A) Receptors Heterodimerization and Cellular Effectors (Ca2+, ERK 1/2 and p38) Activation
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- Radoi, Vlad (författare)
- Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
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- Jakobsson, Gerd (författare)
- Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linköping, Sweden.
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- Palada, Vinko (författare)
- Univ Helsinki, Fac Med, Dept Physiol, SleepWell Res Program, Helsinki 00290, Finland.
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- Nikosjkov, Andrej (författare)
- Karolinska Institutet
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- Druid, Henrik (författare)
- Karolinska Institutet
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- Terenius, Lars (författare)
- Karolinska Institutet
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- Kosek, Eva (författare)
- Karolinska Institutet,Uppsala universitet,Klinisk smärtforskning,Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
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- Vukojevic, Vladana (författare)
- Karolinska Institutet
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Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linköping, Sweden. (creator_code:org_t)
- 2022-04-06
- 2022
- Engelska.
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 27:7
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The importance of the dynamic interplay between the opioid and the serotonin neuromodulatory systems in chronic pain is well recognized. In this study, we investigated whether these two signalling pathways can be integrated at the single-cell level via direct interactions between the mu-opioid (MOP) and the serotonin 1A (5-HT1A) receptors. Using fluorescence cross-correlation spectroscopy (FCCS), a quantitative method with single-molecule sensitivity, we characterized in live cells MOP and 5-HT1A interactions and the effects of prolonged (18 h) exposure to selected non-peptide opioids: morphine, codeine, oxycodone and fentanyl, on the extent of these interactions. The results indicate that in the plasma membrane, MOP and 5-HT1A receptors form heterodimers that are characterized with an apparent dissociation constant K-d(app) = (440 +/- 70) nM). Prolonged exposure to all non-peptide opioids tested facilitated MOP and 5-HT1A heterodimerization and stabilized the heterodimer complexes, albeit to a different extent: K-d,Fentanyl(app) = (80 +/- 70) nM), K-d,FMorphine(app) = (200 +/- 70) nM, K-d,Codeine(app) = (100 +/- 70) nM and K-d,(app)(Oxycodone) = (200 +/- 70) nM. The non-peptide opioids differed also in the extent to which they affected the mitogen-activated protein kinases (MAPKs) p38 and the extracellular signal-regulated kinase (Erk1/2), with morphine, codeine and fentanyl activating both pathways, whereas oxycodone activated p38 but not ERK1/2. Acute stimulation with different non-peptide opioids differently affected the intracellular Ca2+ levels and signalling dynamics. Hypothetically, targeting MOP-5-HT1A heterodimer formation could become a new strategy to counteract opioid induced hyperalgesia and help to preserve the analgesic effects of opioids in chronic pain.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- chronic pain
- fluorescence cross-correlation spectroscopy (FCCS)
- G protein-coupled receptor (GPCR)
- opioid
- serotonin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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