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The properties of ryanodine‐sensitive Ca2+ release in mouse gastric smooth muscle cells
Open accessAbstract
Under voltage‐clamped conditions, gastric smooth muscle cells of BALB/c mice developed spontaneous (STOCs) and caffeine‐ (ICAF) and carbachol‐induced (ICCh) transient outward currents. In fura‐2 microscopic measurements of intracellular Ca 2+ concentration ([Ca 2+]i), caffeine and carbachol (CCh) provoked similar transient [Ca 2+]i elevations. Both ICCh and CCh‐induced [Ca 2+]i elevation of single smooth muscle cells occurred in an ‘all‐or‐nothing’ fashion in contrast to the reproducible caffeine responses. On the basis of the suppression of STOCs and ICAF by nicardipine, tetraethylammonium and iberiotoxin, but not by charybdotoxin nor apamin, it was suggested that both currents were generated by large conductance type Ca 2+‐activated K+ channels. In measurements of isometric tension, caffeine produced relaxation of gastric smooth muscle strips in a concentration‐dependent manner (0.1 – 3 m M). The concentration‐dependent relaxation with caffeine was mimicked by dibutyryl cyclic AMP which produced potentiation of contraction triggered by 50 m M KCl. At caffeine concentrations >3 m M, a transient contraction followed by relaxation was provoked as the quasi maximal response to caffeine. In the quasi maximal response, caffeine acted as a potent relaxant in smooth muscle strips precontracted with 50 m M KCl or 3 μ M CCh. The relaxation with caffeine was significantly accelerated in those strips precontracted with KCl or CCh. All these results suggest that ryanodine‐sensitive Ca 2+ release, which is triggered by caffeine, is an important modifier of Ca 2+ homeostasis in the cytoplasm and the contractility of gastric smooth muscle cells of mice. British Journal of Pharmacology (2001) 133, 125–137; doi:10.1038/sj.bjp.0704048
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In vitro, caffeine's effects on gastrointestinal smooth muscle are dose-dependent: low doses (0.1-0.3 mM) relax and high doses (>0.3 mM) produce a transient contraction followed by relaxation.
“In these experiments, the effects of caffeine were shown to be dose-dependent, with low doses (0.1–0.3 mM) relaxing and high doses (>0.3 mM) producing a transient contraction followed by relaxation [160].”
From Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis (2020) · cites this paper as [160]
In “Effects of caffeine on smooth muscle contractility” (page unavailable), the paper reports reduced tone at concentrations above 0.3 mM, but a transient contraction followed by relaxation only at concentrations above 3 mM—not throughout the claimed >0.3 mM range. It also reports that low concentrations (0.1–0.3 mM) caused transient contractions in strips precontracted with high potassium, so the low-dose description depends on experimental conditions. (LLM, conf=0.88)
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References 49 · Cited by 13
Research works printed but not linked: 2
- SHAW B.A., 1992, A role for kinase/phosphatase action in the regulation of brain amino acid receptors, Mol. Pharmacol., 2, 297
- 10.1210/en.138.5.2056 · DOI
Metadata
- Authors
- Tokutomi, Y., Tokutomi, N., & Nishi, K.
- Affiliations
- Kumamoto University (JP)
- Corresponding author
- Tokutomi, Naofumi
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2001-05
- Volume
- 133
- Issue
- 1
- Pages
- 125-137
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1572764
- OpenAlex
- W1998352336
- Cited by
- 13
- References
- 49
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2015: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (10670090)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- caffeine, gastric smooth muscle, calcium-activated potassium channels, transient outward current, intracellular calcium, carbachol, nicardipine, iberiotoxin, tetraethylammonium, cyclic AMP, smooth muscle relaxation, muscle contraction, calcium homeostasis, all-or-nothing response
- MeSH terms
- Animals, Caffeine, Calcium, Carbachol, Cells, Cultured, Bucladesine, Dose-Response Relationship, Drug, Electric Conductivity, Gastric Mucosa, Isometric Contraction, Mice, Inbred BALB C, Muscle Relaxation, Muscle, Smooth, Nicardipine, Potassium, Potassium Chloride, Ryanodine, Stomach, Potassium Channels, Ion Channel Gating, Fura-2, Tetraethylammonium, Potassium Channels, Calcium-Activated, Large-Conductance Calcium-Activated Potassium Channels, Mice, In Vitro Techniques
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