dexniguldipine and Neuroblastoma

The effects of nifedipine, niguldipine, nimodipine and nitrendipine on the high K+-induced intracellular Ca2+ ([Ca2+]i) transient in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells were studied by using the fluorescent Ca2+ indicator fura-2. It was observed that nifedipine at the concentration of 50 microM inhibited the high K+-induced [Ca2+]i transient by about 60%; niguldipine at the concentration of 10 microM caused a reduction of about 65% in the high K+-induced calcium signal and a further increase in the concentration up to 50 microM did not result in a significant further reduction in the high K+-induced calcium signal. However, on the other hand, nimodipine and nitrendipine at 50 microM inhibited almost completely the high K+-induced [Ca2+]i transient. Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels.

Topics: Animals; Bucladesine; Calcium; Calcium Channel Blockers; Calcium Channels; Cell Differentiation; Dihydropyridines; Evoked Potentials; Glioma; Hybrid Cells; Kinetics; Mice; Neuroblastoma; Nimodipine; Nitrendipine; Potassium; Rats

Digital imaging fluorescence microscopy was used to investigate the effect of the B subunit of cholera toxin on calcium homeostasis in neuroblastoma N18 cells. The B subunit, which binds specifically to ganglioside GM1 in the outer leaflet of the cell membrane, was found to induce a sustained increase of intracellular calcium concentration ([Ca2+]i). The increase in [Ca2+]i was not observed in the absence of extracellular calcium, or in the presence of the calcium chelator EGTA, and was blocked by nickel. The B subunit was also found to induce an influx of manganese ions, as indicated by a quench of the intracellular fura-2 fluorescence. These data suggest that the B subunit induces an increase in calcium influx in N18 cells. Potassium-induced depolarization also stimulated manganese influx; however, after the onset of depolarization-induced influx, the B subunit had no further effect. This occlusion suggests involvement of voltage-dependent calcium channels. Treatment with BayK8644, a dihydropyridine agonist selective for L-type calcium channels, induced manganese influx that was not altered by the B subunit and apparently blocked the effect of the B subunit itself. Furthermore, the dihydropyridine L-type channel antagonists niguldipine or nicardipine completely inhibited B subunit-induced manganese influx. Thus, the B subunit-induced manganese influx is likely due to activation of an L-type voltage-dependent calcium channel. Spontaneous influx of manganese ions was also inhibited by nicardipine or niguldipine and by exogenous gangliosides. Ganglioside GM1 was more potent than GM3, but globoside had no significant effect. The modulation of L-type calcium channels by endogenous ganglioside GM1 has important implications for its role in neural development, differentiation, and regeneration and also for its potential function in the electrical excitability of neurons.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Cell Line; Cholera Toxin; Dihydropyridines; Egtazic Acid; Fura-2; G(M1) Ganglioside; G(M3) Ganglioside; Manganese; Mice; Microscopy, Fluorescence; Neuroblastoma; Nicardipine; Nickel; Potassium; Tumor Cells, Cultured