Bradykinin evokes a Ca2+-activated chloride current in non-neuronal cells isolated from neonatal rat dorsal root ganglia.
We have studied the effect of bradykinin (Bk) on fibroblast-like satellite (FLS) cells isolated from cultures of neonatal rat dorsal root ganglia (DRG). In voltage-clamped FLS cells Bk evoked an inward current response that was concentration dependent with a half-maximal concentration of 2 nM. In indo-1 AM-loaded FLS cells Bk evoked a rise in intracellular Ca2+ that was concentration dependent with a half-maximal concentration of 1 nM. The FLS cells still produced an inward current in response to Bk in the absence of extracellular Ca2+ but the response was inhibited if the intracellular concentration of EGTA was increased from 0.5 to 5 mM, which suggests that the inward current was dependent on the release and subsequent rise of intracellular Ca2+. The reversal potential of the Bk-induced inward current was consistent with the current being due to an increase in Cl- conductance and shifted in a Nernstian manner when the intracellular Cl- concentration was reduced. The inward current response to Bk was blocked by the B2 receptor antagonist HOE-140, which indicates that the response was due to activation of B2 receptors. The data suggest that Bk evokes a rise in intracellular Ca2+ and activation of a Ca2+-activated Cl- conductance in the FLS cells and raise the possibility that FLS cells contribute to the pro-inflammatory effects of Bk in DRG.
England
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Novartis Institute for Medical Research, 5 Gower Place, London WC1E 6BN, UK.
Heblich
F
F
James
I F
IF
Robbins
J
J
Docherty
R J
RJ
D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018118:Chloride Channels; D004533:Egtazic Acid; C065679:icatibant; D001920:Bradykinin; D002118:Calcium