Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways.
In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to IK,BK, through activation of a calcium-dependent potassium current. In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins. Here, we have investigated the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and occluded both actions of BK, and both effects were insensitive to pertussis toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin-insensitive G protein.
Wilk-Blaszczak
M A
MA
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas 75235.
Gutowski
S
S
Sternweis
P C
PC
Belardetti
F
F
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005910:Glioma; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006822:Hybrid Cells; D007700:Kinetics; D008954:Models, Biological; D009447:Neuroblastoma; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013779:Tetrodotoxin; D004743:Enkephalin, Leucine; D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D001920:Bradykinin