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Volume 270, Number 5, Issue of February 3, 1995 pp. 1992-1999
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Effects of Bradykinin and Endothelin-1 on the Calcium Homeostasis of Mammalian Cells

(Received for publication, May 20, 1994; and in revised form, October 21, 1994)

Ursula Quitterer Christian Schröder Werner Müller-Esterl Hubert Rehm

Ca mobilization from intracellular stores is a major event in the signaling cascade triggered by peptide hormone receptors. The transient rise in intracellular free Ca concentration ([Ca]) is well characterized, but little is known about alterations of total cell Ca. Therefore we established a technique to determine changes in total cell Ca during hormone stimulation of Ca-loaded cells. Bradykinin and endothelin-1 reduced total cell Ca by up to 56% in HF-15 cells, COS-7 cells, and CHO K1 cells transfected with the rat B2 receptor cDNA. In Rat-1 cells and PC-12 cells, stimulation with endothelin-1 or bradykinin did not result in a net decrease in total cell Ca at physiological extracellular Ca concentration. Decrease in total cell Ca was preceded by an increase in [Ca] and blunting of the transient rise in [Ca] by a Ca chelator prevented the hormone-induced decrease in total cell Ca. Previous reduction of total cell Ca by one hormone suppressed the transient rise in [Ca] induced by another. The data present evidence that the hormones bradykinin and endothelin-1 are capable of switching off the Ca-mobilizing signal transduction pathway in a cell by depleting intracellular Ca stores. This process is accompanied by a significant reduction of total cell Ca.




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