Nerve growth factor action on membrane permeation to exogenous substrates in dorsal root ganglionic dissociates from...

An experimental system has been described, in previous studies, where the ability of chick embryo dorsal root ganglionic cells to incorporate radiouridine into RNA declines in the absence of nerve growth factor (NGF), and is promptly restored by delayed supply of the factor. Following these early and fully reversible events, further NGF deprivation causes progressive irreversible damage. The early decline in RNA labeling and its reversion by NGF are accompanied by similar changes in the accumulation of acid-soluble radioactivity from the exogenous radiouridine substrate. In the present study, it is shown that the NGF-dependent accumulation of "soluble" radiomaterials is independent from, and responsible for, the NGF-dependent alterations in RNA labeling. Both changes are measurable with labeled cytidine and guanosine, as well as uridine, and in all cases accumulation of acid-precipitable and acid-soluble radioactivities are strictly proportional to each other. The acid-soluble responses to NGF are not prevented by actinomycin D or cycloheximide treatments, demonstrating that they require neither ongoing syntheses of RNA or protein nor prior effects of NGF on them. Chromatography of acid-soluble radiopools showed that the NGF-dependent increase was not due to a distortion in the intracellular phosphorylation of uridine; but involved corresponding increases in all the radiouridine derivatives including UTP. The time patterns of the acid-soluble response were comparable to those of the RNA labeling response, and maximal NGF effects occurred within minutes of its presentation. Finally, 2-deoxyglucose and a-aminoisobutyric acid, but not leucine, showed NGF-dependent accumulation patterns similar to those of the 3 nucleosides. It is proposed that regulation of selected membrane permeation properties could be the primary process through which NGF exerts its trophic role.