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Neurogenetics

In contrast to the increasing neurogenetic data on human gliomas, little is known on their cellular physiological properties. We investigated the potential of these cells to respond to ligands specific or prevailing in the central nervous system. With the aid of a laser scanning microscope, intracellular Ca2+ signalling (using the fluorescent dye Fluo-3) was used as a screening system for neuroligand receptors. Cells in primary culture from five glioblastomas, three astrocytomas, three oligodendrogliomas, and one neurocytoma were tested for their responsiveness to 0.1 mM of ATP, histamine, serotonin, norepinephrine, substance P, glutamate, GABA, and 0.01 mM of angiotensin II and bradykinin, and 50 mM K+ as a mean to induce membrane depolarization and thus detect the presence of voltage gated Ca2+ channels. The response pattern in astrocytoma and glioblastoma cells was similar, however, individual cells were more heterogeneous. Sensitivity was high to histamine and ATP, and lower or negative to the other ligands. The oligodendrogliomas differed from astroglial tumors in that (i) cells were not as responsive to ATP and showed virtually no reactions to glutamate, GABA, membrane depolarization or norepinephrine, and (ii) individual cells exhibited a more uniform response pattern. All neurocytoma cells showed a calcium increase after membrane depolarization indicating the presence of voltage gated Ca2+ channels, in contrast to oligodendroglial and most astrocytic tumors. Our results indicate that the different types of gliomas can be distinguished from each other and from neurocytoma by their repertoire of receptors coupled to calcium signalling. Moreover, we consider histamine the most promising candidate as a receptive element for modulating tumor cell properties.

Supported by the Deutsche Forschungsgemeinschaft (Pa 519-1-1/1-2).


Headings
neurotransmitter mediated Ca2+ signalling
glioblastom
astrocytom
oligodendrogliom
neurocytom

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