5-Methylnicotinamide inhibits renal brush-border phosphate transport with no change in NAD.
Administration of nicotinamide to rats produces a dose-dependent increase in nicotinamide adenine dinucleotide (NAD) content in the renal cortex and specific inhibition of sodium gradient-dependent phosphate transport across the renal brush-border membrane (BBM). Nicotinamide acts both as a precursor for NAD synthesis and as an inhibitor of NAD hydrolysis. To determine if the latter effect contributes to the change in phosphate transport, a nicotinamide analogue was used in the present study. 5-Methylnicotinamide (5MN) cannot support NAD synthesis, but it is an equipotent inhibitor of NAD-hydrolyzing enzymes. The characteristics of the specific inhibitory effect of nicotinamide on sodium gradient-dependent phosphate transport were reproduced by an equimolar dose (4 mmol/kg body wt) of 5MN. Unlike nicotinamide, the action of 5MN did not involve a change in renal cortical NAD content. These data indicate that inhibition of NAD hydrolyzing enzymes may be associated with inhibition of BBM phosphate transport, and this effect occurs independently of changes in NAD levels. These conclusions are supported by the finding that BBM phosphate transport was not inhibited by administration of nicotinic acid, an analogue that does not inhibit NAD hydrolysis.
D000818:Animals; D001692:Biological Transport; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010280:Parathyroid Glands / Q000502:physiology; D010710:Phosphates / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism / Q000502:physiology; D013965:Thyroidectomy
D010710:Phosphates; D009243:NAD; D009536:Niacinamide; D009525:Niacin; C024785:5-methylnicotinamide; D012964:Sodium