ArticlePloS one2014
δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Disease Severity- and Hormonal Status-Dependent Alterations of EGF and MIF in the Serum of Endometriosis Patients.International journal of molecular sciences · 2025Article
- Exploring key features of selectivity in somatostatin receptors through molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine.Frontiers in pharmacology · 2024Article
- Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities.Life (Basel, Switzerland) · 2021Article
- Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist.Life (Basel, Switzerland) · 2021Article
- Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism.Endocrine · 2020Article
- Novel Drug-Like Somatostatin Receptor 4 Agonists are Potential Analgesics for Neuropathic Pain.International journal of molecular sciences · 2019Article
- The human brain somatostatin interactome: SST binds selectively to P-type family ATPases.PloS one · 2019Article
- Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes.Nature communications · 2018Article
- The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain.Frontiers in pharmacology · 2018Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Treating pain with somatostatin receptor subtype 4 agonists.ACS medicinal chemistry letters · 2015Article
- Colocalization of cannabinoid receptor 1 with somatostatin and neuronal nitric oxide synthase in rat brain hypothalamus.Journal of molecular neuroscience : MN · 2015Article
- Delta-opioid receptor analgesia is independent of microglial activation in a rat model of neuropathic pain.PloS one · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Pain relief is the principal action of opioids. Somatostatin (SST), a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4). In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that SSTR4 and δ-Opioid receptor (δOR) exist in a heteromeric complex and function in synergistic manner. SSTR4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of SSTR4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of cAMP/PKA and co-activation of SSTR4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of SSTR4. Inhibition of cAMP/PKA and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between SSTR4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of SST in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.
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