The role of calcium in cell shrinkage and intracellular alkalinization by bradykinin in Ha‐ras oncogene expressing cells

FEBS Letters

Lang, F.³  Wöll, E.²  Scholz, W.¹  Häussinger, D.⁴  Ritter, M.² 

[1] Hoechst AG, Frankfurt, Germany;Institute for Physiology, University of Innsbruck, Innsbruck, Austria;Institute for Physiology, University of Tübingen, Tübingen, Germany;Department of Internal Medicine, University of Freiburg, Freiburg, Germany

关键词: Intracellular calcium;    ras oncogene;    Bradykinin;    Cell volume;    Na+/H+ exchanger;   

DOI  :  10.1016/0014-5793(93)81583-L

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown