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Cycloheximide blocks nicotinamide action on phosphate excretion in thyroparathyroidectomized rats
K I Wu1, R A Bacon, S A Kempson
1Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis.
Mineral and Electrolyte Metabolism
|January 1, 1988
Summary
Nicotinamide inhibits phosphate reabsorption in the kidneys. While it directly impacts proximal tubule uptake, its broader phosphaturic effect requires protein synthesis, suggesting action in other nephron segments.
Area of Science:
- Nephrology
- Renal Physiology
- Molecular Biology
Background:
- Nicotinamide is known to inhibit renal phosphate (Pi) reabsorption.
- This inhibition is observed as decreased Na+-dependent Pi uptake in brush border membrane (BBM) vesicles and increased urinary Pi excretion.
Purpose of the Study:
- To investigate the role of protein synthesis in nicotinamide's effect on renal phosphate handling.
- To determine if nicotinamide's inhibitory action on phosphate reabsorption occurs in multiple nephron segments.
Main Methods:
- Using thyroparathyroidectomized (TPTX) rats adapted to a low-Pi diet.
- Administering cycloheximide (CHX), a protein synthesis inhibitor, before nicotinamide treatment.
- Measuring Na+-dependent Pi uptake in BBM vesicles and urinary Pi excretion.
Main Results:
- Cycloheximide (CHX) pretreatment did not affect nicotinamide's inhibition of Pi uptake by BBM vesicles.
- CHX pretreatment completely blocked the phosphaturic response to nicotinamide.
- Nicotinamide's inhibition of Pi reabsorption extends beyond the proximal convoluted tubule to other sites like the pars recta or distal tubules.
Conclusions:
- Nicotinamide's inhibition of phosphate reabsorption in the proximal convoluted tubule is independent of protein synthesis.
- Nicotinamide's action on other nephron segments, leading to phosphaturia, is dependent on protein synthesis.
- These findings suggest a complex, site-specific mechanism for nicotinamide's effect on renal phosphate handling.