Mechanism of α,β-dehydrolovastatin (DHLV) actions on cAMP-dependent CFTR activity in intestinal epithelial T84 cell monolayers.

(A) Schematic diagrams showing the regulatory mechanism of CFTR Cl- channel activity. (B) Effect of DHLV on cAMP-dependent Cl- secretion determined by apical ICl- analysis induced by forskolin (20 μM), genistein (20 μM), or CPT-cAMP (100 μM). The involvement of phosphodiesterase (PDE) and multidrug-resistance 4 (MRP4) was determined by 15 min pre-treatment with IBMX (1 mM) or MK571 (20 μM), respectively, prior to forskolin treatment. Representative ISC tracings are shown. (C) Summary of concentration-inhibition studies. Data are fitted to Hill’s equation and expressed as means of % agonist-stimulated ICl- ± S.E.M. (n = 3–7). (D) Effect of DHLV on intracellular cAMP levels. T84 cells were pre-treated with vehicle (control) or DHLV (20 μM) for an hour. Intracellular cAMP levels were measured by cAMP parameter assay kits. Data are expressed as concentrations of cAMP ± S.E.M. (n = 3). NS, non-significant compared with indicated group.