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Requirement of Intact Adenosine A1 Receptors for the Diuretic and Natriuretic Action of the Methylxanthines Theophylline and Caffeine
Abstract
Although the diuretic and natriuretic effects of the methylxanthines caffeine and theophylline are well established, the mechanisms responsible for these effects are unclear and may be related to inhibition of phosphodiesterases and/or antagonism of adenosine receptors. With regard to the latter, pharmacological blockade of A1 receptors can induce diuresis and natriuresis by inhibition of proximal tubular reabsorption. To elucidate the role of the A1 receptor in renal actions of methylxanthines, experiments were performed in A1 receptor knockout (A1R-/-) and littermate wild-type (A1R+/+) mice. Urinary excretion was determined in awake mice in metabolic cages over 3 h in response to theophylline (as theophylline2/ethylenediamine, 45 mg/kg), caffeine (45 mg/kg), or vehicle (0.9 ml/30 g b.wt. of 0.85% NaCl) given by oral gavage. Theophylline and caffeine elicited a diuresis and natriuresis (in absolute terms and related to urinary creatinine excretion) in A1R+/+ but not in A1R-/- mice. In a second series, the renal effect of intravenous application of theophylline (30 mg/kg) was determined in clearance experiments under anesthesia. This study revealed that the blunted diuretic and natriuretic effect of theophylline in A1R-/- mice was not due to different responses in blood pressure or glomerular filtration rate. The data indicate that an intact A1 receptor is necessary for caffeine- and theophylline-induced inhibition of renal reabsorption causing diuresis and natriuresis. This is consistent with the assumption that A1 receptor blockade mediates these effects.
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Metadata
- Authors
- Rieg, T., Steigele, H., Schnermann, J., Richter, K., Osswald, H., & Vallon, V.
- Affiliations
- University of Tübingen (DE)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 313
- Issue
- 1
- Pages
- 403-409
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2134391819
- Cited by
- 133
- References
- 43
- Citations by year
- 2025: 9 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 19 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 4
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Keywords
- adenosine A1 receptor, theophylline, caffeine, methylxanthines, diuresis, sodium excretion, tubular reabsorption, phosphodiesterase inhibition, urinary excretion
- MeSH terms
- Anesthesia, Animals, Caffeine, Diuretics, Genotype, Glomerular Filtration Rate, Mice, Inbred C57BL, Natriuresis, Potassium, Sodium, Theophylline, Urodynamics, Mice, Knockout, Receptor, Adenosine A1, Mice
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