Calcium signaling induced by bradykinin is synergistically enhanced by high K+ in NG108-15 cells.
We report a novel phenomenon in which the cytosolic Ca2+ concentration ([Ca2+]i) rise induced in neuroblastoma x glioma hybrid NG108-15 cells by bradykinin is synergistically enhanced by elevated extracellular K+ concentrations. Presence of extracellular Ca2+ during high-K+ treatment, but not after high-K+ treatment, was required for the synergism. In addition, when thapsigargin was added concurrently with high K+, bradykinin still induced a significantly higher [Ca2+]i rise than in cells treated with thapsigargin only. Both bradykinin-induced inositol 1,4,5-trisphosphate (IP3) generation and the size of the internal Ca2+ pool were increased by high-K+ treatment. Our data suggest that changes in membrane potential itself induced by high K+ probably do not cause the synergistic effect. The synergistic effect is apparently due to the stimulatory effects of high K+ on [Ca2+]i, which in turn modulates IP3 generation and increases the size of intracellular Ca2+ pools. If bradykinin is added following high K+, the synergism can be accounted for by increases both in IP3 production and in the size of the internal Ca2+ pools. If bradykinin is added simultaneously with high K+, enhanced Ca2+ release triggered by enhanced IP3 production is the major cause of the synergistic effects.
Chueh
S H
SH
Department of Biochemistry, National Defense Medical Center, Academia Sinica, Taipei, Taiwan, Republic of China.
Kao
L S
LS
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006822:Hybrid Cells / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004533:Egtazic Acid; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D011188:Potassium; D001920:Bradykinin; D002118:Calcium