Physiol. Res. 51: 73-78, 2002

Functional Cross-talk of Ca2+-Mobilizing Endothelin Receptors in C6 Glioma Cells


1Joint Laboratory of Cancer Cell Biology of the First Institute of Medical Chemistry and Biochemistry, First Faculty of Medicine, Charles University, and Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Received January 29, 2001
Accepted May 2, 2001

There are conflicting results concerning the receptor subtype(s) involved in calcium-mediated endothelin signaling in the glial cells. In order to elucidate the role of endothelin A and B receptors in these processes, we have studied the effect of a complex spectrum of endothelin receptor ligands on intracellular calcium concentration changes in proliferating and differentiated C6 rat glioma cells. Cell differentiation was induced by dibutyryl-cAMP and assessed by the glial fibrillar acidic protein content. Intracellular calcium changes were measured in cell suspensions using fluorescent probe Fura-2. The specific endothelin B receptor agonists sarafotoxin S6c and IRL-1620 did not influence the intracellular calcium concentration. However, calcium changes induced by endothelin-1 and especially by endothelin-3 after the pretreatment of cells with one of these endothelin B receptor specific agonists were significantly enhanced even above the values attained by the highest effective endothelin concentrations alone. Such endothelin B-receptor ligand-induced sensitization of calcium signaling was not observed in differentiated C6 cells. Moreover, endothelin-induced calcium oscillations in differentiated C6 cells were less inhibited by BQ-123 and BQ-788 than in their proliferating counterparts. In conclusion, the specific activation of endothelin B receptor in C6 rat glioma cells does not affect intracellular calcium per se, but probably does so through interaction with the endothelin A receptor. The pattern and/or functional parameters of endothelin receptors in C6 rat glioma cells are modified by cell differentiation.

Key words
Endothelin receptor · Glioma · Calcium signaling · Cell differentiation

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Aleksi Šedo, First Institute of Medical Chemistry and Biochemistry, First Faculty of Medicine, Charles University, Kateřinská 32, CZ-121 08 Prague 2, Czech Republic, e-mail:

© 2002 by the Institute of Physiology, Czech Academy of Sciences