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• W2015535756 endingPage "1819" @default.
• W2015535756 startingPage "1809" @default.
• W2015535756 abstract "The link between increased usage of β-adrenoceptor agonists and worsening of asthma symptoms has raised interest in the effects of agents such as salbutamol on airway wall remodelling, and particularly airway smooth muscle proliferation. In the present study we have investigated the role of increases in intracellular cAMP in the inhibitory effect of salbutamol on airway smooth muscle proliferation. The inhibitory effects of a combination of submaximally effective concentrations of salbutamol (10 nM) and the non-selective phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 100 μM) on thrombin (0.3 U/mL)-induced mitogenesis in human cultured airway smooth muscle cells was greater than that for either agent alone. In addition, agents known to increase cAMP-dependent protein kinase activity including forskolin (10 μM), 8-bromoadenosine-3′,5′-cyclic monophosphate (100 μM), and prostaglandin E2 (1 μM) have an inhibitory effect on thrombin (0.3 U/mL)-induced proliferation. Furthermore, the cAMP antagonist, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (300 μM) significantly reduced the inhibitory effect of salbutamol (10 nM) on thrombin (0.3 U/mL)-induced DNA synthesis. In IBMX (100 μM)-pretreated cells, salbutamol (100 nM) increased intracellular cAMP levels via stimulation of a β2-adrenoceptor. Salbutamol (10 μM), at concentrations supramaximally effective for inhibition of mitogenesis, had no effect on thrombin (0.3 U/mL)-induced increases in intracellular calcium levels. Therefore, our results suggest that the previously reported inhibition of mitogen-induced proliferation in human cultured airway smooth muscle cells by the β2-adrenoceptor agonist, salbutamol (100 nM), is at least partly due to elevation of intracellular cAMP, while there is no effect of salbutamol on initial mitogen-induced increases in intracellular calcium." @default.
• W2015535756 created "2016-06-24" @default.
• W2015535756 creator A5010376459 @default.
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• W2015535756 date "1995-06-01" @default.
• W2015535756 modified "2023-10-15" @default.
• W2015535756 title "Salbutamol inhibits the proliferation of human airway smooth muscle cells grown in culture: Relationship to elevated cAMP levels" @default.
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• W2015535756 doi "https://doi.org/10.1016/0006-2952(94)00532-q" @default.
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