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.
Quitterer
U
U
Institute for Physiological Chemistry and Pathobiochemistry, Mainz, Germany.
Schröder
C
C
Müller-Esterl
W
W
Rehm
H
H
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D018002:Receptors, Bradykinin / Q000502:physiology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D016232:Endothelins; D018002:Receptors, Bradykinin; D013729:Terpenes; D004533:Egtazic Acid; D019284:Thapsigargin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D001920:Bradykinin; D002118:Calcium