ArticleFrontiers in cellular neuroscience2019
Purinergic Signaling and Aminoglycoside Ototoxicity: The Opposing Roles of P1 (Adenosine) and P2 (ATP) Receptors on Cochlear Hair Cell Survival.
Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 18 citations in OpenAlex.
- [An interpretation of the blue book: the report on hearing health in china (2025)].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2026Article
- Protective Effect of Selegiline (R-deprenyl) in Aminoglycoside-Induced Hearing Loss.Neurochemical research · 2025Article
- Auckland hearing science discovery and translation in purinergic signaling and inner ear therapeutics.Journal of the Royal Society of New Zealand · 2025Review
- Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity.Frontiers in immunology · 2023Article
- Purinergic Signalling in the Cochlea.International journal of molecular sciences · 2022Review
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
- In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Bioinformatic Analysis of the Perilymph Proteome to Generate a Human Protein Atlas.Frontiers in cell and developmental biology · 2022Article
- Istradefylline Mitigates Age-Related Hearing Loss in C57BL/6J Mice.International journal of molecular sciences · 2021Article
- miR‑125/CDK2 axis in cochlear progenitor cell proliferation.Molecular medicine reports · 2021Article
- Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss.International journal of molecular sciences · 2020Article
- Inhibition of the Adenosine ACells · 2019Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purinergic signaling regulates important physiological processes and the homeostatic response to stress in the cochlea via extracellular nucleosides (adenosine) and nucleotides (ATP, UTP). Using a previously established organotypic culture model, the current study investigated the effect of purinergic P1 (adenosine) and P2 (ATP) receptor activation on the survival of the sensory hair cell population in the cochlea exposed to the ototoxic aminoglycoside neomycin. Organ of Corti explants were obtained from C57BL/6 mice at postnatal day 3 (P3) and maintained in normal culture medium (with or without purine receptor agonists or analogs) for 19.5 h prior to neomycin exposure (1 mM, 3 h) followed by a further incubation for 19.5 h in culture medium. The cochlear explants were then fixed in 4% paraformaldehyde (PFA) and sensory hair cells labeled with Alexa 488-phalloidin. Neomycin induced a substantial loss of the sensory hair cells, mostly in the middle segment of the cochlea. This neomycin-induced ototoxicity was unaffected by the addition of P2 receptor agonists (ATP and UTP) in the culture medium, whilst the addition of their slowly-hydrolyzable analogs (ATPγS, UTPγS) aggravated neomycin-induced sensory hair cell loss. In contrast, the activation of P1 receptors by adenosine or adenosine amine congener (ADAC) conferred partial protection from neomycin ototoxicity. This study demonstrates a pro-survival effect of P1 receptor stimulation, whilst prolonged activation of P2 receptors has an opposite effect. Based on these findings, we postulate that P1 and P2 receptors orchestrate differential responses to cochlear injury and that the balance of these receptors is important for maintaining cochlear homeostasis following ototoxic injury.
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