Cycloheximide blocks nicotinamide action on phosphate excretion in thyroparathyroidectomized rats.
Nicotinamide causes marked inhibition of phosphate (Pi) reabsorption in the renal proximal tubule and this can be detected both as a specific decrease in Na+-dependent Pi uptake by isolated brush border membrane (BBM) vesicles and as a marked increase in urinary Pi excretion. In the present study, thyroparathyroidectomized (TPTX) rats were adapted to low-Pi diet and injected with cycloheximide (CHX), an inhibitor of protein synthesis, prior to nicotinamide treatment. Compared to rats that received nicotinamide alone, the pretreatment with CHX did not alter the inhibitory action of nicotinamide on BBM uptake of Pi. However, CHX completely blocked the phosphaturic response. We conclude that, at least in TPTX rats adapted to low-Pi diet, nicotinamide inhibits Pi reabsorption not only in the proximal convoluted tubule but also in other nephron segments such as the pars recta or distal sites. Nicotinamide action on these additional sites is dependent on protein synthesis, in contrast to its action in the proximal convoluted tubule.
Wu
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KI
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis.
Bacon
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RA
Kempson
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SA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000502:physiology*; D010710:Phosphates / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D013965:Thyroidectomy
D010710:Phosphates; D009536:Niacinamide; D003513:Cycloheximide; D012964:Sodium