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A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115-401L neuronal cells.
- Source :
-
The Biochemical journal [Biochem J] 1988 Jul 01; Vol. 253 (1), pp. 81-6. - Publication Year :
- 1988
-
Abstract
- Thapsigargin, a sesquiterpene lactone with potent irritant and tumour-promoting activities, stimulates a rapid (within 15 s) transient increase in intracellular [Ca2+] in the NG115-401L neural cell line, as measured by the fluorescent indicator dye fura-2. This increase in cytoplasmic free [Ca2+] is concentration-dependent (ED50 around 20 nM) and occurs in the absence of extracellular Ca2+. Activation of NG115-401L cells by the inflammatory peptide bradykinin generates inositol phosphates, which parallel increases in intracellular [Ca2+]. However, the rise in cytoplasmic [Ca2+] stimulated by thapsigargin occurs in the absence of detectable production of inositol phosphates. Thapsigargin is unlike phorboid tumour promoters in that it has no action on two non-invasive indicators of phorbol stimulation of these cells, i.e. [3H]choline metabolite production and rise in intracellular pH. These data suggest that thapsigargin releases Ca2+ from an intracellular store by a novel mechanism, independent of the hydrolysis of phosphoinositides and concomitant activation of protein kinase C. Thus thapsigargin may provide a valuable tool for the analysis of intracellular signalling mechanisms.
- Subjects :
- Bradykinin pharmacology
Calcimycin pharmacology
Cell Line
Choline metabolism
Digitonin pharmacology
Intracellular Fluid drug effects
Intracellular Fluid metabolism
Neurons drug effects
Spectrometry, Fluorescence
Thapsigargin
Calcium metabolism
Inositol Phosphates metabolism
Neurons metabolism
Plant Extracts pharmacology
Plants, Medicinal analysis
Sugar Phosphates metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 253
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 3138987
- Full Text :
- https://doi.org/10.1042/bj2530081