Nerve Growth Factor Affects Cyclic AMP Metabolism, but Not by Directly Stimulating Adenylate Cyclase Activity

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Abstract
Whether nerve growth factor (NGF) can regulate adenylate cyclase activity was studied [in rat PC12 pheochromo cytoma cells]. A sensitive assay that measures the conversion of [2-3H]adenine to [3H]cAMP, showed that NGF alone cannot measurably stimulate cAMP production, whereas the adenosine analog phenylisopropyladenosine (PIA) stimulates adenylate cyclase 20-fold over basal activity. NGF potentiates the capacity of both PIA and cholera toxin to stimulate cAMP accumulation at all concentrations tested. This potentiation occurs at the earliest measureable times and does not require RNA synthesis. Apparently cyclase activation alone does not account for the effect of NGF on cAMP accumulation. Possible mechanisms are discussed.