Potentiation by tumour necrosis factor‐α of calcium signals induced by bradykinin and carbachol in human tracheal smooth muscle cells

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Abstract
The effect of tumour necrosis factor-α (TNFα) on the increase in cytosolic free calcium ([Ca2+])i induced by carbachol and bradykinin (BK) was investigated in human tracheal smooth muscle cells in culture (TSMC). BK (10−12–10−9m) and carbachol (10−7–10−3m) produced a concentration-dependent increase in [Ca2+]i (pD2 = 10.73 ± 0.05 and 5.57 ± 0.03 respectively). The increase in [Ca2+]i was significantly enhanced for both agonists in TNFα-treated cells (10 ng ml−1 for 24 h). However, pD2 values were not modified (10.78 ± 0.03 and 5.62 ± 0.04 for BK and carbachol, respectively) suggesting that no change in the apparent receptor affinity occured. Thus, TNFα induced-alterations in Ca2+ homeostasis in human TSMC may be a key mechanism underlying airway hyperreactivity.