Dynamics of NAD in cortical nephron segments: effect of nicotinamide and of dietary phosphate intake.
NAD content and the rate of NAD hydrolysis were determined in proximal convoluted tubules (PCT), proximal straight tubules (PST), and adjacent cortical nephron segments microdissected from kidneys of thyroparathyroidectomized (TPTX) rats. In the basal state, rats fed a normal phosphate diet had an NAD content higher in PCT, PST, and in cortical ascending limb (CAL) than in glomeruli. After intraperitoneal injection of nicotinamide, the NAD content increased significantly in all nephron segments except CAL; the greatest (delta + 277%) increase was found in PCT, with less (delta + 82%) in PST. In experiments conducted on TPTX rats stabilized on a low-phosphorus diet, NAD content increased in response to a nicotinamide injection in PCT (delta + 197%), but did not change significantly in PST. The catabolism of NAD was determined by generation of [3H]adenosine, a major metabolite of [adenine-2,8-3H]NAD. The rate of [3H]adenosine generation from [3H]NAD was significantly (P less than 0.001) higher in PST than in PCT. We conclude that, in response to nicotinamide administration in vivo, the NAD content increases more in PCT than in PST and that this difference may be, at least partly, due to a lower rate of NAD breakdown in PCT. In a state of dietary phosphate deprivation, NAD also increases significantly in response to intraperitoneal nicotinamide in PCT, but it does not increase significantly in PST. The nicotinamide-elicited increase of NAD content in proximal tubules, mainly in PCT, may be related to inhibition of Na+-gradient-dependent inorganic phosphate (Pi) reabsorption across the brush-border membrane of proximal tubules and to the phosphaturic effect of nicotinamide in rats fed normal-Pi diet.
D000818:Animals; D004032:Diet; D009243:NAD / Q000378:metabolism*; D009399:Nephrons / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000502:physiology; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy
D010710:Phosphates; D009243:NAD; D009536:Niacinamide