Opposite regulatory effects of cAMP and cGMP on sugar uptake in rat thymocytes

The present study provides several lines of evidence which indicate that in the rat thymocyte adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5-cyclic monophosphate (cGMP) induce opposing regulatory effects on 2-deoxyglucose (2-DG) uptake; cAMP is stimulatory, whereas cGMP is inhibitory. First, the cyclic nucleotide analogues dibutyryl cAMP (dBcAMP) and dibutyryl cGMP (dBcGMP) produced a dose-related increase and decrease in thymocyte 2-DG uptake, respectively. Second, 3,5,3'-triiodo-L-thyronine (T3) and epinephrine, which increased cellular cAMP concentration but had no effect on cellular cGMP concentration, increased 2-DG uptake in the rat thymocyte. Third, dBcGMP inhibited the stimulatory effects of dBcAMP, T3, and epinephrine on thymocyte 2-DG uptake. Fourth, prostaglandin E1 and the inhibitors of the cyclic nucleotide phosphodiesterases, 3-isobutyl-1-methylxanthine, theophylline, and caffeine, all increased both cellular cAMP and cGMP concentration but had no effect on 2-DG uptake. Insulin did not change cellular cAMP and cGMP concentration, but produced a dose-related increase in 2-DG uptake by the rat thymocyte. From these results I have concluded that in the rat thymocyte cAMP and cGMP produce opposite effects on sugar uptake and that the effect of certain, but not all, agents on thymocyte sugar uptake results from their modulation of cellular cAMP and cGMP concentration.