ArticleAmerican journal of physiology. Renal physiology2015
Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Renal NHE3 is required to limit hypokalemia and metabolic acidosis during dietary potassium deficiency.Pflugers Archiv : European journal of physiology · 2026Article
- Review
- Association between caffeine and the eGFR dip after initiation of SGLT2 inhibitors in adult patients.Physiological reports · 2025Article
- Lack of renal NHE1 exacerbates lithium-induced nephrogenic diabetes insipidus.Acta physiologica (Oxford, England) · 2025Article
- Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses.Kidney international · 2025Article
- Exploring the association between dietary caffeine and chronic musculoskeletal pain: a cross-sectional analysis of NHANES.Frontiers in nutrition · 2025Article
- The S-shaped association between dietary caffeine intake and severe headache or migraine: a cross-sectional study based on NHANES.Frontiers in neurology · 2025Article
- Common questions and misconceptions about caffeine supplementation: what does the scientific evidence really show?Journal of the International Society of Sports Nutrition · 2024Review
- Predictors for poor daily weight gain in preterm neonates exposed to different dose regimens of caffeine in ICU- a retrospective cohort study.BMC pediatrics · 2024Article
- Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.International journal of molecular sciences · 2024Article
- New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024Review
- IntestinalJournal of geriatric cardiology : JGC · 2023Article
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Caffeine causes cell cycle arrest at G0/G1 and increases of ubiquitinated proteins, ATP and mitochondrial membrane potential in renal cells.Computational and structural biotechnology journal · 2023Article
- Green tea and coffee consumption and risk of kidney cancer in Japanese adults.Scientific reports · 2022Article
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification.American journal of physiology. Renal physiology · 2022Article
- The NaFrontiers in physiology · 2022Review
- The association between caffeine intake and risk of kidney stones: A population-based study.Frontiers in nutrition · 2022Article
- Oral Hydration Before and After Hip Replacement: The Notion Behind Every Action.Geriatric orthopaedic surgery & rehabilitation · 2022Article
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na(+)/H(+) exchanger isoform 3 (NHE3) localization and phosphorylation, resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2, and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605, or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na(+)/bicarbonate cotransporter NBCe1, pretreatment with DIDS inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis.
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