England S, Heblich F, James I F, Robbins J, Docherty R J
Novartis Institute for Medical Research, 5 Gower Place, London WC1E 6BN, UK.
J Physiol. 2001 Feb 1;530(Pt 3):395-403. doi: 10.1111/j.1469-7793.2001.0395k.x.
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.
我们研究了缓激肽（Bk）对从新生大鼠背根神经节（DRG）培养物中分离出的成纤维细胞样卫星（FLS）细胞的作用。在电压钳制的FLS细胞中，Bk诱发了内向电流反应，该反应呈浓度依赖性，半数最大浓度为2 nM。在负载indo-1 AM的FLS细胞中，Bk诱发细胞内Ca2+升高，该反应呈浓度依赖性，半数最大浓度为1 nM。在无细胞外Ca2+的情况下，FLS细胞仍对Bk产生内向电流，但如果细胞内EGTA浓度从0.5 mM增加到5 mM，该反应则受到抑制，这表明内向电流依赖于细胞内Ca2+的释放及随后的升高。Bk诱导的内向电流的反转电位与该电流由Cl-电导增加所致一致，并且当细胞内Cl-浓度降低时，以能斯特方式发生偏移。对Bk的内向电流反应被B2受体拮抗剂HOE-140阻断，这表明该反应是由于B2受体的激活。这些数据表明，Bk诱发FLS细胞内Ca2+升高并激活Ca2+激活的Cl-电导，并增加了FLS细胞促成Bk在DRG中的促炎作用的可能性。
