EFFECTS OF NERVE GROWTH FACTOR ON CYCLIC AMP LEVELS IN EMBRYONIC CHICK DORSAL ROOT GANGLIA FOLLOWING FACTOR DEPRIVATION

Nerve growth factor (NGF) at 10 B.U./ml produced a 5-fold increase in the concentration of cyclic AMP 10min after addition to freshly excised embryonic chick dorsal root ganglia (DRG). The presence of NGF at 10 B.U./ml, but not 1 B.U./ml, over a 6 h incubation in nutrient-free medium prevented this cyclic AMP increase when the DRG were again challenged with NGF (10 B.U./ml) after the 6 h. Incubation of DRG for 6 h at 37°C without NGF did not prevent the cyclic AMP response from occurring when NGF was presented at this time. The basal cyclic AMP concentration, however, decreased by 65–75% during the course of the 6 h incubation, and the continuous presence of NGF (10 B.U./ml) was unable to prevent this. When NGF was added to 6-h NGF-deprived DRG, the time for maximum cyclic AMP increase decreased from 15min to 6min with increasing NGF concentrations from 1 to 50 B.U./ml, although the relative magnitude of the cyclic AMP increase was essentially the same (approx 3-fold) at these NGF concentrations. Attempts were made to correlate the cyclic AMP response in NGF-deprived DRG with another rapid response resulting from administration of NGF to NGF-deprived DRG, namely, the reactivation of hexose uptake. The cyclic AMP and permeation responses both occurred on the same time scale (5-15 min), and both responded to increasing concentrations of NGF with a decreasing time to achieve maximal effect. A temporal relationship between cyclic AMP and membrane permeability was noted, but it could not be ruled out that it might reflect difficulties in methodology and/or inadequacy in current knowledge of the underlying mechanisms.