Glioblastoma cells express functional cell membrane receptors activated by daily used medical drugs.
OBJECTIVE
Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology.


METHODS
Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope-camera-computer-unit.


RESULTS
Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors.


CONCLUSIONS
Our study impressively demonstrates that medical drugs are potent inducers of intracellular calcium signals. Totally unexpected, the results show a high amount of functional cellular receptors and channels on glioma cells, which could be responsible for certain biological effects like migration and cell growth. This calcium imaging study proves the usability of the calcium imaging as a screening system for functional receptors on human glioma cells.
Kuhn
Susanne A
SA
Department of Neurosurgery, Medical Center, Friedrich-Schiller-University, Erlanger Allee 101, 07747 Jena, Germany. Susanne.Kuhn@med.uni-jena.de
Mueller
Ulrike
U
Hanisch
Uwe-K
UK
Regenbrecht
Christian R A
CR
Schoenwald
Ilona
I
Brodhun
Michael
M
Kosmehl
Hartwig
H
Ewald
Christian
C
Kalff
Rolf
R
Reichart
Rupert
R
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D004366:Nonprescription Drugs / Q000145:classification / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D004366:Nonprescription Drugs; D011956:Receptors, Cell Surface; D002118:Calcium