Role of cyclic 3',5'-GMP in modulation of cellular uptake of phosphate.

The role of cGMP in regulating renal cortical phosphate uptake was investigated in rats. Cyclic GMP (1 mM) produced a 27.7% +/- 1.4 (SE) increase in 32PO4 uptake by isolated renal cortical tubules (P less than 0.001) and cAMP (1 mM) a 28.7% +/- 1.4 increase (P less than 0.001), but their effects were not additive. Acetylcholine (Ach) (1 mM), in the presence of theophylline (T) (10 mM), increased cGMP in cortical slices from 24.1 pmol/g wet wt +/- 1.3 to 76.5 +/- 5.2 (P less than 0.001), but had no effect on cAMP, and Ach (1 mM) in the presence of T (1 mM) increased 32PO4 uptake 19.1% +/- 1.1 (P less than 0.001). Addition of Ca2+ to the incubation medium in the presence of T (10 mM) significantly increased cGMP in cortical slices from 7.4 pmol/g wet wt +/- 0.6 (0 Ca2+ plus EGTA, 0.5 mM) to 24.1 +/- 1.3 (1 mM Ca2+) and caused a 52.2% +/- 2.7 rise in 32PO4 uptake (P less than 0.001). Cyclic AMP was decreased by the addition of Ca2+. In summary, cGMP and cAMP stimulate 32PO4 uptake by renal cortex, and Ach and Ca2+ increase both cGMP and 32PO4 but do not increase cAMP. These data suggest that cGMP may play a role in regulating cellular uptake of phosphate.