Activated microglia secretome and proinflammatory cytokines increase neuronal mu-opioid receptor signalling and expression.

Autor: Cuitavi J; Instituto de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain., Duart-Abadia P; Instituto de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Valencia, Burjassot, Spain; Departament of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, Burjassot, Spain., Sanchez J; Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, the Midlands, UK., Sánchez-López CM; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain; Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics UV-IIS La Fe, Valencia, Spain., Lorente JD; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain., Marcilla A; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain; Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics UV-IIS La Fe, Valencia, Spain., Fariñas I; Instituto de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Valencia, Burjassot, Spain; Departament of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, Burjassot, Spain., Canals M; Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, the Midlands, UK. Electronic address: M.Canals@nottingham.ac.uk., Hipólito L; Instituto de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain. Electronic address: lucia.hipolito@uv.es.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Dec; Vol. 230 (Pt 3), pp. 116608. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1016/j.bcp.2024.116608
Abstrakt: Due to its potential role in processes which rely on mu-opioid receptor function, investigating the relationship between Mu-Opioid receptors (MORs), neuroinflammation, and glial cells has gained momentum. Traditionally, MOR activation has been associated with immunosuppression, but recent findings suggest a more nuanced, bidirectional relationship with the immune system. To further investigate this relationship, herein, we investigated the role of the activated microglia secretome and proinflammatory cytokines in neuronal MOR expression and signalling. Our results show that both microglial secretome and specific cytokines increase neuronal MOR expression and enhance the [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO)-induced MOR activation. We also show that DAMGO-induced neuroinflammation increases neuronal MOR expression, activation, and regulation. Our findings suggest a feedback loop between microglial activation, cytokine release, and neuronal MOR dynamics. Future research should delve into the temporal dynamics and functional implications of this relationship, particularly concerning clinically relevant opioids like morphine and fentanyl and pain management.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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