CHARACTERISTICS OF THE K-252A-INDUCED INCREASE IN CALCIUM-UPTAKE IN PC12 CELLS

K-252a treatment produced a 30-50% increase in the uptake of radioacti ve calcium by PC12 cells within 3-4 minutes. The increase in uptake wa s partially blocked by inhibitors of voltage-operated calcium channels , such as nifedipine, but not by inhibitors of receptor-operated calci um channels, such as nickel or suramin. Introduction of phosphatase 2A into the cells completely blocked the effect of K-252a. Long-term tre atment of the cells with either K-252a or with nerve growth factor blo cked the subsequent actions of either K-252a or nerve growth factor on calcium uptake, but neither altered the subsequent action of the L-ch annel agonist Bay K 8644 on calcium uptake. Calcium uptake was not sti mulated by K-252a in PC12nnr, cells that have little or no high-affini ty nerve growth factor receptors; cells expressing increased levels of high-affinity nerve growth factor receptors showed a response to K-25 2a comparable to that seen in parent PC12. The data suggest that the i ncreased uptake of radioactive calcium produced by K-252a is mediated by a mechanism very similar to that serving the increased calcium upta ke produced by nerve growth factor. (C) 1995 Wiley-Liss, Inc.