Increased cAMP in proximal tubules is acute effect of nicotinamide analogues.
The possible role of adenosine 3',5'-cyclic monophosphate (cAMP) in the mechanism of the acute inhibitory effects of nicotinamide and analogues on brush-border membrane (BBM) phosphate transport was investigated. Compared with basal values, cAMP content of rat renal proximal tubule suspensions was elevated two- to fivefold when incubated at 37 degrees C for 1 h with nicotinamide, 5-methylnicotinamide, or picolinamide at 1-3 mM and in the presence of a phosphodiesterase inhibitor. Thymidine had no effect on cAMP content. There was significant and specific inhibition of BBM transport of phosphate when proximal tubules were incubated with either nicotinamide or picolinamide at concentrations that increased tubule cAMP content. Thymidine had no effect on BBM transport of phosphate. These findings were independent of the dietary Pi intake of the rats. The absence of any effect of thymidine on phosphate transport strongly suggests that inhibition of poly(adenosine diphosphate ribose) polymerase does not play a role in nicotinamide action on phosphate transport. The change in phosphate transport induced by nicotinamide occurred with no change in NAD content. These findings indicate that an increase in cAMP, rather than NAD, is the important change that may mediate the acute inhibition of Na(+)-dependent phosphate transport by nicotinamide.
Campbell
P I
PI
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
Abraham
M I
MI
Kempson
S A
SA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000494:pharmacology
D010710:Phosphates; D009536:Niacinamide; D000242:Cyclic AMP; D007930:Leucine; D013936:Thymidine