Nicotinamide as a rapid-acting inhibitor of renal brush-border phosphate transport.
Administration of nicotinamide to rats produces specific dose-dependent inhibition of Na+-dependent phosphate transport across the renal brush-border membrane (BBM) and an increase in urinary excretion of phosphate. The intracellular mechanism of action of nicotinamide is not well established. As a step in this direction, the present studies determined whether nicotinamide was a rapid- or slow-acting regulator of the BBM phosphate transport system. Nicotinamide (0.5 g/kg) inhibited Na+-dependent BBM phosphate transport under conditions when de novo protein synthesis was inhibited by cycloheximide (1.0 mg/kg). Furthermore, the degree of inhibition was not different from that achieved by nicotinamide alone, suggesting that the action of nicotinamide does not require de novo protein synthesis. Studies on the time course of the onset of nicotinamide action revealed inhibition of BBM phosphate transport within 1 h after injection of nicotinamide, even in rats pretreated with cycloheximide. The rapid response to nicotinamide and its independence of de novo protein synthesis characterize nicotinamide as a rapid-acting regulator of the Na+-dependent phosphate transport system in renal BBM.
Wu
K I
KI
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
Bacon
R A
RA
Al-Mahrouq
H A
HA
Kempson
S A
SA
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000648:ultrastructure*; D007930:Leucine / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D003609:Dactinomycin; D009536:Niacinamide; D003513:Cycloheximide; D000242:Cyclic AMP; D007930:Leucine