AJP - Renal Physiology, Vol 257, Issue 6 1021-F1026, Copyright © 1989 by American Physiological Society
Increased cAMP in proximal tubules is acute effect of nicotinamide analogues
P. I. Campbell, M. I. Abraham and S. A. Kempson
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
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.
