Maitotoxin-induced nerve growth factor production accompanied by the activation of a voltage-insensitive Ca2+ channel in C6-BU-1 glioma cells

1 The aim of the present study was to determine the effects of maitotoxin o n nerve growth factor production and the Ca2+ influx in clonal rat glioma c ells (CG-BU-1). 2 Maitotoxin (1-10 ng ml(-1)) induced a profound increase in Ca-45(2+) infl ux in an extracellular Ca2+-dependent manner. However, high KCl had no effe ct at all. These effects were supported by the results from the analysis of intracellular Ca2+ concentration using fura 2. 3 The maitotoxin-indufed Ca-45(2+) influx was inhibited by inorganic Ca2+ a ntagonists, such as Mg2+, Mn2+ and Co2+ The inhibitory effect of Co2+ was a ntagonized by increasing the extracellular Ca2+ concentrations. 4 Maitotoxin (3 ng ml(-1)) as well as A-23187 (1 mu M) and dibutyryl cyclic AMP (0.5 mM) caused an acceleration of nerve growth factor (NGF) productio n in C6-BU-1 cells, as determined by NGF enzyme immunoassay. 5 Reverse transcription polymerase chain reaction (RT-PCR) analysis showed that maitotoxin (10 ng ml(-1)) enhanced the expression of NGF mRNA, which w as abolished by the removal of extracellular Ca2+. A-23187 also accelerated its expression. 6 These results suggest that maitotoxin activates a voltage-insensitive Ca2 + channel and accelerates NGF production mediated through a Ca2+ signalling pathway in C6-BU-1 glioma cells.