The role of potassium channels in the inhibitory effects of beta(2)-adrenoceptor agonists on DNA synthesis in human cultured airway smooth muscle

Opening of calcium-dependent K+ channels by beta(2)-adrenoceptor agonists has been shown to contribute to their smooth muscle relaxant activity, In this study, the influence of K+ channel activity on human cultured airway smooth muscle proliferation and on its inhibition by salbutamol have been examined, Studies of Rb-86(+) efflux from the airway smooth muscle cell cultures confirmed that both cromakalim, an activator of ATP-dependent K+ channels and salbutamol increased K+ channel activity in cultured airway smooth muscle, The efflux of Rb-86(+) was significantly attenuated by non-specific K+ channel blockade, Potassium channel blockers had only small and variable effects on [H-3]-thymidine incorporation in unstimulated cells and those stimulated with fetal calf serum (FCS) and no effect on FCS-induced increases in cell number, Potassium channel openers also had no substantial inhibitory effects on DNA synthesis or proliferation in cells stimulated with other mitogens including thrombin, Blockade of K+ channels had no consistent effects on the inhibition of DNA synthesis and cell proliferation caused by salbutamol (0.3 nM-10 mu M). The inhibition of DNA synthesis caused by 8 bromoadenosine 3'5' cyclic monophosphate (1 mu M-1 mM) or 8 bromoguanosine 3'5' cyclic monophosphate (1 mu M-1 mM) was also unaffected by K+ channel blockade, These results indicate that changes in K+ channel activity have no detectable influence on DNA synthesis and proliferation of human cultured airway smooth muscle cells or on the antiproliferative effects of beta(2)-agonists. (C) 1997 Academic Press Limited.