دورية أكاديمية
Trimethoprim inhibits renal H+/K+ ATPase in states of K+ depletion
| العنوان: | Trimethoprim inhibits renal H+/K+ ATPase in states of K+ depletion |
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| المؤلفون: | Ayasse, Niklas, Berg, Peder, Svendsen, Samuel L, Rousing, Amalie Quist, Sørensen, Mads Vaarby, Fedosova, Natalya U, Leipziger, Jens |
| المصدر: | Ayasse , N , Berg , P , Svendsen , S L , Rousing , A Q , Sørensen , M V , Fedosova , N U & Leipziger , J 2024 , ' Trimethoprim inhibits renal H+/K+ ATPase in states of K+ depletion ' , American journal of physiology. Renal physiology , vol. 326 , no. 1 , pp. F143-F151 . https://doi.org/10.1152/ajprenal.00273.2023Test |
| سنة النشر: | 2024 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | Acidosis/metabolism, Animals, Anti-Bacterial Agents/pharmacology, Epithelial Sodium Channels/metabolism, H(+)-K(+)-Exchanging ATPase/metabolism, Kidney Tubules, Collecting/metabolism, Mice, Sodium/metabolism, Swine, Trimethoprim/pharmacology, metabolic acidosis, sulfamethoxazole, benzamil, epithelial Na+ channel |
| الوصف: | There is growing consensus that under physiological conditions, collecting duct H+ secretion is independent of epithelial Na+ channel (ENaC) activity. We have recently shown that the direct ENaC inhibitor benzamil acutely impairs H+ excretion by blocking renal H+-K+-ATPase. However, the question remains whether inhibition of ENaC per se causes alterations in renal H+ excretion. To revisit this question, we studied the effect of the antibiotic trimethoprim (TMP), which is well known to cause K+ retention by direct ENaC inhibition. The acute effect of TMP (5 µg/g body wt) was assessed in bladder-catheterized mice, allowing real-time measurement of urinary pH, electrolyte, and acid excretion. Dietary K+ depletion was used to increase renal H+-K+-ATPase activity. In addition, the effect of TMP was investigated in vitro using pig gastric H+-K+-ATPase-enriched membrane vesicles. TMP acutely increased natriuresis and decreased kaliuresis, confirming its ENaC-inhibiting property. Under control diet conditions, TMP had no effect on urinary pH or acid excretion. Interestingly, K+ depletion unmasked an acute urine alkalizing effect of TMP. This finding was corroborated by in vitro experiments showing that TMP inhibits H+-K+-ATPase activity, albeit at much higher concentrations than benzamil. In conclusion, under control diet conditions, TMP inhibited ENaC function without changing urinary H+ excretion. This finding further supports the hypothesis that the inhibition of ENaC per se does not impair H+ excretion in the collecting duct. Moreover, TMP-induced urinary alkalization in animals fed a low-K+ diet highlights the importance of renal H+-K+-ATPase-mediated H+ secretion in states of K+ depletion.NEW & NOTEWORTHY The antibiotic trimethoprim (TMP) often mediates K+ retention and metabolic acidosis. We suggest a revision of the underlying mechanism that causes metabolic acidosis. Our results indicate that TMP-induced metabolic acidosis is secondary to epithelial Na+ channel-dependent K+ retention. Under control dietary ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://pure.au.dk/portal/en/publications/60fcdc2d-2327-4f03-ad8f-567b59054aadTest |
| DOI: | 10.1152/ajprenal.00273.2023 |
| الإتاحة: | https://doi.org/10.1152/ajprenal.00273.2023Test https://pure.au.dk/portal/en/publications/60fcdc2d-2327-4f03-ad8f-567b59054aadTest |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.B72ECDE8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1152/ajprenal.00273.2023 |
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