Cindrić, S.; Bodenbeck, L.; Hjeij, R.; Loges, N.T.; Edelbusch, C.; Pennekamp, P.; Rieger-Fackeldey, E.; Omran, H. Caffeine Citrate Increases Ciliary Beat Frequency in Human Respiratory Epithelial Cells. Preprints2023, 2023040386. https://doi.org/10.20944/preprints202304.0386.v1
APA Style
Cindrić, S., Bodenbeck, L., Hjeij, R., Loges, N.T., Edelbusch, C., Pennekamp, P., Rieger-Fackeldey, E., & Omran, H. (2023). Caffeine Citrate Increases Ciliary Beat Frequency in Human Respiratory Epithelial Cells. Preprints. https://doi.org/10.20944/preprints202304.0386.v1
Chicago/Turabian Style
Cindrić, S., Esther Rieger-Fackeldey and Heymut Omran. 2023 "Caffeine Citrate Increases Ciliary Beat Frequency in Human Respiratory Epithelial Cells" Preprints. https://doi.org/10.20944/preprints202304.0386.v1
Abstract
Since 2000, caffeine is used as citrate salt of caffeine for treatment of apnea of prematurity. However, it remained elusive if caffeine citrate has a direct function in the respiratory epithelium, potentially as modulator for ciliary beat frequency (CBF) regulation in human respiratory cells (hRECs). Here, we studied the mechanism of action of caffeine citrate on the respiratory epithelium on hRECs derived from healthy donors and individuals with cystic fibrosis (CF) cultured under air-liquid-interface (ALI) conditions. CBF analyses of hRECs were performed by high-speed video microscopy. In the presence of caffeine, hRECs show a significant increase in CBF over ciliary base frequency (CBFb), demonstrating a direct influence of caffeine on ciliary function. We also demonstrate a specific action of caffeine at ryanodine receptor (RYR) channels, mediating calcium efflux from intracellular stores to increase CBF. We describe a novel pharmacological effect of caffeine citrate - direct increase of CBF of primary hRECs cultured at ALI. Caffeine citrate has certain advantages over other methylxanthines: it was shown to have stable plasma concentration, longer half-life, and is better tolerated than e.g. theophylline. We conclude that caffeine citrate therapy might be suitable strategy to treat respiratory diseases with compromised mucociliary clearance.
Medicine and Pharmacology, Pediatrics, Perinatology and Child Health
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