Neuroligand-mediated calcium signaling in cultured human schwannoma cells.

Intracellular Ca2+ release regulates proliferation of nonexcitable cells, however, it is not known whether and which neuroligands modulate the free intracellular Ca2+ concentration in human schwannoma cells. Confocal laser scanning microscopy was used for the study of neuroligand-induced Ca2+ signaling in cultured human schwannoma cells loaded with the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during bath application of ATP (90% of cells tested), endothelin (60%), and norepinephrine (20%); histamine, serotonin, glutamate, and bradykinin did not have this effect. Two types of P2Y nucleotide receptor subtypes involved in ATP-induced Ca2+ transients could be separated by application of different P2Y receptor agonists and cross desensitization experiments: P2Y1 (rank order of potency: 2-MeSADP > 2-MeSATP > ADP > ATP) and P2Y2 (sensitive to UTP and ATP). Endothelin-induced Ca2+ signaling was also seen during application of [Ala(1,3,11,15)]ET-1; this suggests the presence of an ET(B) receptor subtype. The results indicate that the presence of receptors linked to neuroligand-triggered Ca2+ signaling does not seem to be abnormal in a human Schwann cell tumor, i.e. schwannoma cells retain this characteristic of peripheral glia.