Effects of bradykinin and endothelin-1 on the calcium homeostasis of mammalian cells.

Ca2+ mobilization from intracellular stores is a major event in the signaling cascade triggered by peptide hormone receptors. The transient rise in intracellular free Ca2+ concentration ([Ca2+]i) 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 45Ca-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 Ca2+ concentration. Decrease in total cell Ca was preceded by an increase in [Ca2+]i and blunting of the transient rise in [Ca2+]i by a Ca2+ chelator prevented the hormone-induced decrease in total cell Ca. Previous reduction of total cell Ca by one hormone suppressed the transient rise in [Ca2+]i induced by another. The data present evidence that the hormones bradykinin and endothelin-1 are capable of switching off the Ca(2+)-mobilizing signal transduction pathway in a cell by depleting intracellular Ca stores. This process is accompanied by a significant reduction of total cell Ca.