Figure 3. Continuous exposure to albuterol reduces stimulated CFTR activity in a fashion similar to continuous or intermittent dosing with formoterol.

wtCFTR⁺ and VX809-corrected F508del-CFTR⁺ CFBE41o- cells were exposed to either continuous or intermittent (1 hour, twice daily) albuterol (10 μM) or the long-acting β2AR-agonist formoterol (LABA; 1 μM) for 72 hours. Cells were mounted in Ussing chambers and CFTR function was assessed under voltage clamp conditions. (A) Representative short-circuit current (I_sc) tracings in wtCFTR⁺ CFBE41o- cells exposed for 72 hours to either continuous (C) or intermittent (I) albuterol or formoterol; aggregate data are presented in B (n = 4 inserts/condition; circles represent total CFTR activity [cAMP + genistein], diamonds represent inhibited CFTR currents [Inh172]). (C) Representative I_sc tracings in VX809-treated F508del-CFTR⁺ CFBE41o- cells exposed for 72 hours to either continuous (C) or intermittent (I) albuterol or formoterol; aggregate data are presented in D (n = 4 inserts/condition). All data were normalized to the control or VX809 (no albuterol pretreatment) condition. Stimulation protocol was as follows: amiloride (100 μM, not shown), cAMP (10 μM forskolin/100 μM IBMX; dark gray bars), CFTR potentiator (50 μM genistein for wtCFTR⁺, 1 μM VX770 for F508del-CFTR⁺ cells; light gray bars), and CFTR inhibition (10 μM Inh172; white bars). All experiments are representative of studies repeated in duplicate or triplicate with similar results. Data presented represent the mean ± SEM. *P < 0.05; **P < 0.01; ****P < 0.0005; NS, nonsignificant by 2-way ANOVA with Tukey’s multiple comparisons test.