The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells.
Open Access
- 1 March 1986
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 102 (3), 821-829
- https://doi.org/10.1083/jcb.102.3.821
Abstract
Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3'',5''-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differential effects on the activation of cAMP-dependent protein kinases, i.e., (Sp)-cAMPS behaves as a cAMP agonist and (Rp)-cAMPS behaves as a cAMP antagonist. Our data show that the establishment of a neuritic network, as observed from PC12 cells treated with NGF alone, could not be induced by either forskolin, cAMP, or cAMP analogues alone. The presence of NGF in combination with forskolin or cAMP or its agonistic analogues potentiated the initiation of neurite outgrowth from PC12 cells. The (Sp)-cAMPS-induced stimulation of NGF-mediated process formation was successfully blocked by the (Rp)-cAMPs diastereomer. On the other hand, NGF-stimulated neurite outgrowth was not inhibited by the presence of the cAMP antagonist (Rp)-cAMPs. We conclude that the morphological differentiation of PC12 cells stimulated by NGF does not require cAMP as a second messenger. The constant increase of intracellular cAMP, caused by either forskolin or cAMP and the analogues, in combination with NGF, not only rapidly stimulated early neurite outgrowth but also exerted a maintaining effect on the neuronal network established by NGF.This publication has 29 references indexed in Scilit:
- In Vitro Phosphorylation of Microtubule‐Associated Protein 2: Differential Effects of Cyclic AMP AnaloguesJournal of Neurochemistry, 1985
- Modulation of protein synthesis by nerve growth factor.Journal of Biological Chemistry, 1979
- Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factorProceedings of the National Academy of Sciences, 1978
- Alterations in the surface properties of cells responsive to nerve growth factorNature, 1978
- ADENOSINE 3'-5'-MONOPHOSPHATE RECEPTOR PROTEINS IN MAMMALIAN BRAIN1978
- Alteration of cellular adhesion by nerve growth factor.Proceedings of the National Academy of Sciences, 1977
- Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proceedings of the National Academy of Sciences, 1976
- Nerve growth factor and its mode of actionExperimental Neurology, 1975
- Permeation of dibutyryl cAMP into HeLa cells and its conversion to monobutyryl cAMPBiochemical and Biophysical Research Communications, 1972
- Nerve growth factor.Physiological Reviews, 1968