Comparison of the effects of thapsigargin, 2,5-di-(tertbutyl)- 1,4-hydroquinone and cyclopiazonic acid on calcium release from rat liver endoplasmic reticulum
Abstract
The effects of three novel intracellular Ca2+-ATPase inhibitors on Ca2+ efflux from rat liver endoplasmic
reticulum (ER) were compared. The three inhibitors: thapsigargin (TG); 2,5-di-(tert-butyl)-1,4-hydroquinone (DBHQ) and
cyclopiazonic acid (CPA) released Ca2+ to various extents from the ER. Thapsigargin caused a slow but extensive release of
Ca2+ from the ER, releasing almost all the Ca2+ accumulated by the vesicles during the uptake phase. The other two
inhibitors did not release all the Ca2+ accumulated during the uptake phase. Furthermore, cyclopiazonic acid did not prevent
the re-uptake of the Ca2+ added after the release process. These findings suggest that there may be some intracellular Ca2+
stores which are insensitive to DBHQ and cyclopiazonic acid
Downloads
References
Tada, M.; Yamamoto, T. and Tonomura, Y. (1978) Molecular mechanism of active calcium transport by
sarcoplasmic reticulum. Physiol. Rev. 58, 1 - 79.
Carafoli, E. and Cropmton, M. (1978) The regulation of intracellular calcium. Curr. Topics Membr. Transp. 10,
- 216.
Cheung, W. Y. (1980) Calmodulin plays a pivotal role in cellular regulation. Science 207, 19 - 27.
Carafoli, E. (1987) Intracelular calcium homeostasis. Ann. Rev. Biochem. 56, 395 - 433.
Lehninger, A. L.; Vercesi, A. and Bababunmi, E. A. (1978) Regulation of Ca2+ release from mitochondria
by the oxidation-reduction state of pyridine nucleotides. Proc. Natl. Acad. Sci. (USA) 75, 1690 - 1694.
Carafoli, E. and Sottocasa, G. (1984) The uptake and the release of calcium by mitochondria. In: Bioenergetics, (Ernster, L. ed.), pp. 269 - 289. Elsevier Science Publishers, Amsterdam.
Muallem, S.; Schoeffield, M.; Pandol, S. and Sachs, G. (1985) Inositol trisphosphate modification of ion
transport in rough endoplasmic reticulum. Proc. Natl. Acad. Sci. (USA) 82, 4433 - 4437.
Kijima, Y.; Ogunbunmi, E. and Fleischer, S. (1991) Drug action of thapsigargin on the Ca2+ pump protein
of sarcoplasmic reticulum. J. Biol. Chem. 266, 22912 -22918.
Lytton, J.; Westlin, M. and Hanley, M. R. (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J. Biol. Chem. 266, 17067 - 17071.
Kirby, M. S.; Sagara, Y.; Gaa, S.; Inesi, G.; Lederer, W. J. and Rogers, T. B. (1992) Thapsigargin inhibits
contraction and Ca2+ transient in cardiac cells by specific inhibition of the sarcoplasmic reticulum Ca2+ pump. J. Biol. Chem. 267, 12545 - 12551.
Thastrup, O.; Foder, B. and Scharff, O. (1987) The calcium mobilizing and tumor promoting agent,
thapsigargin elevates the platelet cytoplasmic free calcium concentration to a higher steady state level. A possible mechanism of action for the tumor promotion. Biochem. Biophys. Res. Commun. 142, 654 - 660.
Robinson, I. M. and Burgoyne, R. D. (1991) A distinct 2, 5- di-(tert-butyl) -1,4-benzohydroquinone-sensitive calcium store in bovine adrenal chromaffin cells. FEBS Lett. 289, 151 - 154.
Demaurex, N.; Lew, D. P. and Krause, K. H. (1992) Cyclopiazonic acid depletes intracellular Ca2+ stores
and activates an influx pathway for divalent cations in HL-60 cells. J. Biol. Chem. 267, 2318 - 2324.
Bewaji, C. O. (1995) Ionic requirements for inositol trisphosphate- and thapsigargin-induced Ca2+ release
from rat liver endoplasmic reticulum. Nig. J. Biochem. Mol. Biol. 10, 1 - 6.
Lowry, O. H.; Rosebrough, N. J.; Farr, A. L. and Randall, R. J. (1951) Protein measurement with the
Folin phenol reagent. J. Biol. Chem. 193, 265 - 275.
Dawson, A. P. (1985) GTP enhances inositol trisphosphate-stimulated Ca2+ release from rat liver
microsomes. FEBS Lett. 185(1), 147 - 150.
Oldershaw, C. A., Nunn, D. L. and Taylor, C. W. (1991) Quantal Ca2+ mobilization stimulated by inositol 1,4,5-trisphosphate in permeabilized hepatocytes. Nature (London) 278, 705 - 708.
Irvine, R. F. (1990) Quantal Ca2+ release and the control of Ca2+ entry by inositol phosphates - a
possible mechanism. FEBS Lett. 263, 5 - 9.
Muallem, S.; Pandol, S. J. and Beeker, T. G. (1989) Hormone-evoked calcium release from intracellular
stores is a quantal process. J. Biol. Chem. 264, 205 -212.
Bootman, M. D.; Berridge, M. J. and Taylor, C. W. (1992) All-or-nothing Ca2+ mobolization from the
intracellular stores of single histamine-stimulated HeLa cells. J. Physiol. 450, 163 - 178.
Additional Files
Published
Issue
Section
Categories
License
Copyright (c) 2023 Clement O. Bewaji

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.