POTENTIATION BY TUMOR-NECROSIS-FACTOR-ALPHA OF CALCIUM SIGNALS INDUCED BY BRADYKININ AND CARBACHOL IN HUMAN TRACHEAL SMOOTH-MUSCLE CELLS

The effect of tumour necrosis factor-alpha (TNF alpha) 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(-9) M) and carbachol (10(-7)-10(-3) M) produced a concentration-dependent increase in [Ca2+](i) (pD(2) = 10.73 +/- 0.05 and 5.57 +/- 0.03 respectively). The increase in [Ca2+](i) was significantly enhanced for both agonists in TNF alpha-treated cells (10 ng ml(-1) for 24 h). However, pD(2) 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, TNF alpha induced-alterations in Ca2+ homeostasis in human TSMC may be a key mechanism underlying airway hyperreactivity.