| One of the major signal transduction systems found in all higher eucaryotic cells is the phosphoinositide (PI) turnover pathway. This system is activated in response to many different signals, including growth factors, peptide hormones, and neurotransmitters. Activation of PI turnover causes changes in free cytosolic calcium, (Ca;Bradykinin, a nine residue peptide, is particularly potent in stimulating PI turnover. Prior exposure to NGF greatly potentiates the increase in (Ca;I investigated the cellular mechanisms by which this potentiation is produced. In long-term NGF-treated cells, the bradykinin-induced peak (Ca;Bradykinin-induced calcium release from internal stores was also potentiated by NGF since part of the heightened response persisted in the absence of extracellular calcium. This effect was not due to changes in phosphoinositide turnover since treatment with NGF had no effect on the accumulation of inositol phosphates. Our results demonstrate that there are large changes in the sensitivity to a PI agonist during neuronal differentiation in vitro.;When PC12 cells are treated with nerve growth factor (NGF), they leave the cell cycle and take on many of the characteristics of sympathetic neurons. The advantage to using PC12 cells is that one can apply the techniques of biochemistry and cell biology, allowing us to directly address hypotheses not testable in vivo. |
