Fig. 4.

CF tissues fail to produce basal ASL secretion. a CFTR^−/− swine (CF, n = 9 from six animals) display lower basal ASL secretion than wild-type in vivo (n = 10 from seven animals, mean ± SEM, P = 0.001, Mann–Whitney test). b Wild-type ex vivo preparations with surgically removed submucosal glands (SMG) produced lower basal ASL (n = 12 with SMG from six preparations and n = 13 without SMG from six preparations, P < 0.0001, Mann–Whitney test). c Wild-type ex vivo preparations incubated with CFTRinh172 (100 µM) produced lower basal ASL than non-treated preparations (n = 6 from four preparations for control, and n = 14 from five preparations for CFTRinh172, P < 0.0001, Mann–Whitney test). d Topical application of lidocaine (Lido) had a small effect on basal ASL secretion. Simultaneous treatment with the CFTR inhibitor (Lido + inh172) completely blocked basal ASL secretion (n = 13 control from five preparations, n = 21 Lido from eight preparations, and n = 16 Lido + inh172 from seven preparations; P < 0.0001, F(2, 47) = 59.35, ANOVA and Tukey’s multiple comparison test). e Tetrodotoxin (1 µM, TTX) treatment had no effect on basal ASL secretion (n = 18 control from eight preparations, and n = 11 TTX from four preparations, P = 0.58, Mann–Whitney test). Atropine had no effect on basal ASL secretion in f ex vivo preparations (10 µM, n = 8 without atropine from three preparations and n = 8 with atropine from four preparations, P = 0.76, t = 0.30, df = 14, Student’s t test) or g in vivo wild-type swine (treated with 0.04 mg/kg IM 2–10 min following induction of anesthesia, n = 8 without Atropine from six animals, and n = 10 with Atropine from seven animals, P = 0.75, t = 0.32, df = 16, Student’s t test). h Treatment with SQ22536 (0.5 mM) blocked ASL secretion (n = 10 control from four preparations and n = 11 SQ22536 from four preparations; P = 0.0003, Mann–Whitney test). Data is presented as mean ± SEM and within each panel the columns labeled with an asterisk differ significantly