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 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) or 8 bromoguanosine 3'5' cyclic monophosphate (1 microM-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.
Gillzan
K M
KM
Bernard O'Brien Institute of Microsurgery, St Vincent's Hospital, Fitzroy, Victoria, Australia.
Stewart
A G
AG
D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019806:Cromakalim / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D012413:Rubidium / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D015221:Potassium Channels; D018343:Receptors, Adrenergic, beta-2; D019806:Cromakalim; D004247:DNA; D000242:Cyclic AMP; D012413:Rubidium; D000420:Albuterol