A fixed 20:1 combination of cafedrine/theodrenaline increases cytosolic Ca2+ concentration in human tracheal epithelial cells via ryanodine receptor-mediated Ca2+ release Article Swipe
Götz Schmidt
,
Gerrit Rienas
,
Sabrina Müller
,
Katrin Richter
,
Michael Sander
,
Christian Koch
,
Michael Henrich
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-43342-0
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-43342-0
Mucociliary clearance is a pivotal physiological mechanism that protects the lung by cleaning the airways from pollution and colonization, thereby preventing infection. Ciliary function is influenced by various signal transduction cascades, and Ca 2+ represents a key second messenger. A fixed 20:1 combination of cafedrine and theodrenaline has been widely used to treat perioperative hypotension and emergency hypotensive states since the 1960s; however, its effect on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) of respiratory epithelium remains unknown. Therefore, human tracheal epithelial cells were exposed to the clinically applied 20:1 mixture of cafedrine/theodrenaline and the individual substances separately. [Ca 2+ ] i was assessed by FURA-2 340/380 fluorescence ratio. Pharmacological inhibitors were applied to elucidate relevant signal transduction cascades, and reverse transcription polymerase chain reaction (RT-PCR) was performed on murine tracheal epithelium to analyze ryanodine receptor (RyR) subtype expression. All three pharmacological preparations instantaneously induced a steep increase in [Ca 2+ ] i that quickly returned to its baseline value despite the persistence of each substance. Peak [Ca 2+ ] i following the administration of 20:1 cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone increased in a dose-dependent manner, with median effective concentrations of 0.35 mM (7.32 mM cafedrine and 0.35 mM theodrenaline), 3.14 mM, and 3.45 mM, respectively. When extracellular Ca 2+ influx was inhibited using a Ca 2+ -free buffer solution, the peak [Ca 2+ ] i following the administration of cafedrine alone and theodrenaline alone were reduced but not abolished. No alteration in [Ca 2+ ] i compared with baseline [Ca 2+ ] i was observed during β-adrenergic receptor inhibition. Depletion of caffeine-sensitive stores and inhibition of RyR, but not IP 3 receptors, completely abolished any increase in [Ca 2+ ] i . However, [Ca 2+ ] i still increased following the depletion of mitochondrial Ca 2+ stores using 2,4-dinitrophenol. RT-PCR revealed RyR-2 and RyR-3 expression on murine tracheal epithelium. Although our experiments showed that cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone release Ca 2+ from intracellular stores through mechanisms that are exclusively triggered by β-adrenergic receptor stimulation, which most probably lead to RyR activation, clinical plasma concentrations are considerably lower than those used in our experiments to elicit an increase in [Ca 2+ ] i ; therefore, further studies are needed to evaluate the ability of cafedrine/theodrenaline to alter mucociliary clearance in clinical practice.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-023-43342-0
- https://www.nature.com/articles/s41598-023-43342-0.pdf
- OA Status
- gold
- Cited By
- 4
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4387081317
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https://openalex.org/W4387081317Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41598-023-43342-0Digital Object Identifier
- Title
-
A fixed 20:1 combination of cafedrine/theodrenaline increases cytosolic Ca2+ concentration in human tracheal epithelial cells via ryanodine receptor-mediated Ca2+ releaseWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-09-27Full publication date if available
- Authors
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Götz Schmidt, Gerrit Rienas, Sabrina Müller, Katrin Richter, Michael Sander, Christian Koch, Michael HenrichList of authors in order
- Landing page
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https://doi.org/10.1038/s41598-023-43342-0Publisher landing page
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https://www.nature.com/articles/s41598-023-43342-0.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.nature.com/articles/s41598-023-43342-0.pdfDirect OA link when available
- Concepts
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Ryanodine receptor, Extracellular, Signal transduction, Fura-2, Intracellular, Receptor, Cytosol, Second messenger system, Chemistry, Respiratory epithelium, Internal medicine, Respiratory system, Cell biology, Endocrinology, Biology, Medicine, Biochemistry, EnzymeTop concepts (fields/topics) attached by OpenAlex
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4Total citation count in OpenAlex
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2025: 1, 2024: 3Per-year citation counts (last 5 years)
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43Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.dose-dependent | 189 |
| abstract_inverted_index.Pharmacological | 113 |
| abstract_inverted_index.instantaneously | 147 |
| abstract_inverted_index.pharmacological | 145 |
| abstract_inverted_index.theodrenaline), | 204 |
| abstract_inverted_index.2,4-dinitrophenol. | 304 |
| abstract_inverted_index.caffeine-sensitive | 267 |
| abstract_inverted_index.cafedrine/theodrenaline | 96, 381 |
| abstract_inverted_index.cafedrine/theodrenaline, | 180, 320 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5009891567 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I200763008 |
| citation_normalized_percentile.value | 0.73263769 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |