ArticleBritish journal of pharmacology2014
Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- IL17 signaling promotes oocyte developmental competence acquisition during maturation.Cellular & molecular biology letters · 2026Article
- Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation.International journal of molecular sciences · 2025Review
- Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.CNS neuroscience & therapeutics · 2025Review
- Connexin 43 is downregulated in advanced Parkinson's disease in multiple brain regions which correlates with symptoms.Scientific reports · 2025Article
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Astroglial Connexin 43-Mediated Gap Junctions and Hemichannels: Potential Antidepressant Mechanisms and the Link to Neuroinflammation.Cellular and molecular neurobiology · 2023Review
- Connexin 43 Phosphorylation: Implications in Multiple Diseases.Molecules (Basel, Switzerland) · 2023Review
- Neuroprotective astroglial response to neural damage and its relevance to affective disorders.Exploration of neuroprotective therapy · 2023Article
- Astroglial Connexins Inactivation Increases Relapse of Depressive-like Phenotype after Antidepressant Withdrawal.International journal of molecular sciences · 2022Article
- Connexin 43: insights into candidate pathological mechanisms of depression and its implications in antidepressant therapy.Acta pharmacologica Sinica · 2022Review
- Immediate Early Gene c-fos in the Brain: Focus on Glial Cells.Brain sciences · 2022Review
- Stress-Induced Depression and Alzheimer's Disease: Focus on Astrocytes.International journal of molecular sciences · 2022Review
- Astroglia in the Vulnerability to and Maintenance of Stress-Mediated Neuropathology and Depression.Frontiers in cellular neuroscience · 2022Review
- Effects of an Atypical Antipsychotic, Zotepine, on Astroglial L-Glutamate Release through Hemichannels: Exploring the Mechanism of Mood-Stabilising Antipsychotic Actions and Antipsychotic-Induced Convulsion.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Distinct Effects of Escitalopram and Vortioxetine on Astroglial L-Glutamate Release Associated with Connexin43.International journal of molecular sciences · 2021Article
- Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing.International journal of molecular sciences · 2021Review
- Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43.International journal of molecular sciences · 2021Article
- Astroglial Connexin43 as a Potential Target for a Mood Stabiliser.International journal of molecular sciences · 2020Review
- Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies.Apoptosis : an international journal on programmed cell death · 2019Article
- Intracellular inflammatory and antioxidant pathways in postmortem frontal cortex of subjects with major depression: effect of antidepressants.Journal of neuroinflammation · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIntercellular communication via gap junctions, comprised of connexin (Cx) proteins, allow for communication between astrocytes, which in turn is crucial for maintaining CNS homeostasis. The expression of Cx43 is decreased in post-mortem brains from patients with major depression. A potentially novel mechanism of tricyclic antidepressants is to increase the expression and functioning of gap junctions in astrocytes. EXPERIMENTAL APPROACH: The effect of amitriptyline on the expression of Cx43 and gap junction intercellular communication (GJIC) in rat primary cultured cortical astrocytes was investigated. We also investigated the role of p38 MAPK intracellular signalling pathway in the amitriptyline-induced expression of Cx43 and GJIC. KEY
resultsTreatment with amitriptyline for 48 h significantly up-regulated Cx43 mRNA, protein and GJIC. The up-regulation of Cx43 was not monoamine-related since noradrenaline, 5-HT and dopamine did not induce Cx43 expression and pretreatment with α- and β-adrenoceptor antagonists had no effect. Intracellular signalling involved p38 MAPK, as amitriptyline significantly increased p38 MAPK phosphorylation and Cx43 expression and GJIC were significantly blocked by the p38 inhibitor SB 202190. Furthermore, amitriptyline-induced Cx43 expression and GJIC were markedly reduced by transcription factor AP-1 inhibitors (curcumin and tanshinone IIA). The translocation of c-Fos from the cytosol and the nucleus of cortical astrocytes was increased by amitriptyline, and this response was dependent on p38 activity. CONCLUSION AND IMPLICATION: These findings indicate a novel mechanism of action of amitriptyline through cortical astrocytes, and further suggest that targeting this mechanism could lead to the development of a new class of antidepressants.
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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.