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The role of calcium in cell shrinkage and intracellular alkalinization by bradykinin in Ha‐ras oncogene expressing cells
Author(s) -
Wöll E.,
Ritter M.,
Scholz W.,
Häussinger D.,
Lang F.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81583-l
Subject(s) - bradykinin , intracellular , calcium in biology , calcium , chemistry , shrinkage , oncogene , cell , microbiology and biotechnology , endocrinology , biochemistry , biology , cell cycle , materials science , receptor , organic chemistry , composite material
In ras oncogene expressing cells, bradykinin leads to intracellular alkalinization by activation of the Na + /H + exchanger. This effect is paralleled by oscillatory increase of intracellular calcium activity and cell shrinkage. Staurosporine (1 μmol/l) is not sufficient to prevent bradykinin induced intracellular alkalinization, thus pointing to a protein kinase C independent pathway for the activation of Na + /H + exchange. The present study has been performed to elucidate, whether the increase of intracellular calcium contributes to cell shrinkage and activation of the Na + /H + exchanger. To this end, the effects of the calcium ionophore ionomycin have been tested. Ionomycin leads to a dose dependent increase of intracellular calcium activity. At 100 nmol/l ionomycin intracellular calcium is increased from 114 ± 17 nmol/l to 342 ± 24 nmol/l ( n = 9), a value within the range of intracellular calcium concentrations following application of bradykinin. The calcium increase is paralleled by a decrease of cell volume by 12 ± 2% ( n = 5) and an increase of intracellular pH from 6.78 ± 0.02 to 6.90 ± 0.03 ( n = 11), values similar to those following application of bradykinin. The alkalinizing effect of ionomycin is completely abolished in the presence of the novel Na + /H + exchange inhibitor HOE 694 (10 μmol/l), but is not inhibited by 1 μmol/l staurosporine. Inhibition of K + and Cl − channels by barium (5 mmol/l) and ochratoxin‐A (5 μmol/l) prevents both ionomycin induced cell shrinkage and protein kinase C independent intracellular alkalinization. It is concluded that bradykinin leads to intracellular alkalinization mainly by increasing intracellular calcium concentration. Calcium triggers calcium sensitive K + channels, and presumably Cl − channels, the subsequent loss of cellular KCl leads to cell shrinkage which, in turn, activates Na + /H + exchange.