ArticleMolecular pharmacology2011
Gi/o-coupled receptors compete for signaling to adenylyl cyclase in SH-SY5Y cells and reduce opioid-mediated cAMP overshoot.
Article in Molecular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Casomorphine-10 (CM-10) Peptide Orchestrates Circadian and Neurodevelopmental Gene Clusters via δ-Opioid Receptor Signaling: Insights from Transcriptome Analysis with δ-Opioid Receptor-Expressing HEK293 Cells.Life (Basel, Switzerland) · 2025Article
- A sensitive biosensor of endogenous GαScience signaling · 2025Article
- Endogenous μ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice.PNAS nexus · 2023Article
- Article
- Revealing the Activity of Trimeric G-proteins in Live Cells with a Versatile Biosensor Design.Cell · 2020Article
- Simultaneous Activation of Mu and Delta Opioid Receptors Reduces Allodynia and Astrocytic Connexin 43 in an Animal Model of Neuropathic Pain.Molecular neurobiology · 2019Article
- μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells.Neuroscience · 2019Article
- Role of the guanine nucleotide binding protein, GαPsychopharmacology · 2018Article
- Localization of the delta opioid receptor and corticotropin-releasing factor in the amygdalar complex: role in anxiety.Brain structure & function · 2017Article
- The delta opioid receptor tool box.Neuroscience · 2016Review
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Dynorphin inhibits basal forebrain cholinergic neurons by pre- and postsynaptic mechanisms.The Journal of physiology · 2016Article
- Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later.European journal of pharmacology · 2015Review
- The μ-opioid receptor: an electrophysiologist's perspective from the sharp end.British journal of pharmacology · 2015Review
- Heterologous regulation of Mu-opioid (MOP) receptor mobility in the membrane of SH-SY5Y cells.The Journal of biological chemistry · 2014Article
- 5-HT1A receptor-mediated phosphorylation of extracellular signal-regulated kinases (ERK1/2) is modulated by regulator of G protein signaling protein 19.Cellular signalling · 2014Article
- Modulation of μ-opioid receptor signaling by RGS19 in SH-SY5Y cells.Molecular pharmacology · 2013Article
- μ-Opioid receptor desensitization: homologous or heterologous?The European journal of neuroscience · 2012Article
- Cys-27 variant of human δ-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization.The Journal of biological chemistry · 2012Article
- Cyproheptadine enhances the I(K) of mouse cortical neurons through sigma-1 receptor-mediated intracellular signal pathway.PloS one · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Organization of G protein-coupled receptors and cognate signaling partners at the plasma membrane has been proposed to occur via multiple mechanisms, including membrane microdomains, receptor oligomerization, and protein scaffolding. Here, we investigate the organization of six types of Gi/o-coupled receptors endogenously expressed in SH-SY5Y cells. The most abundant receptor in these cells was the μ-opioid receptor (MOR), the activation of which occluded acute inhibition of adenylyl cyclase (AC) by agonists to δ-opioid (DOR), nociceptin/orphanin FQ peptide (NOPr), α2-adrenergic (α2AR), cannabinoid 1, and serotonin 1A receptors. We further demonstrate that all receptor pairs share a common pool of AC. The MOR agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) also occluded the ability of DOR agonist to stimulate G proteins. However, at lower agonist concentrations and at shorter incubation times when G proteins were not limiting, the relationship between MOR and DOR agonists was additive. The additive relationship was confirmed by isobolographic analysis. Long-term coadministration of MOR and DOR agonists caused cAMP overshoot that was not additive, suggesting that sensitization of AC mediated by these two receptors occurs by a common pathway. Furthermore, heterologous inhibition of AC by agonists to DOR, NOPr, and α2AR reduced the expression of cAMP overshoot in DAMGO-dependent cells. However, this cross-talk did not lead to heterologous tolerance. These results indicate that multiple receptors could be tethered into complexes with cognate signaling proteins and that access to shared AC by multiple receptor types may provide a means to prevent opioid withdrawal.
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