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

Pulmonary Pharmacology & Therapeutics
K M Gillzan, A G Stewart

Abstract

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 86Rb+ 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 86Rb+ was significantly attenuated by non-specific K+ channel blockade. Potassium channel blockers had only small and variable effects on [3H]-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 microM). The inhibition of DNA synthesis caused by 8 bromoadenosine 3'5' cyclic monophosphate (1 microM-1 mM) o...Continue Reading

Citations

Jun 23, 2007·American Journal of Respiratory Cell and Molecular Biology·Malcolm C ShepherdAlastair G Stewart

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