抄録
Patients with cystic fibrosis (CF;cystic fibrosis transmembrane conductance regulator) caused by CFTR gene mutations often fail to produce alkaline pancreatic juice, in which Na+-H+ exchangers (NHE) may be involved. We examined the activity of apical NHE in interlobular pancreatic ducts isolated from δF mice, a CF mouse model. The ducts (diameter:100 μm) were isolated by microdissection and superfused with HCO3−-free Hepes-buffered solutions at 37°C and the lumen was microperfused separately. Intracellular pH (pHi) was measured by microfluorometry using BCECF. Duct cells were acid-loaded with a pulse of 20 mM NH4+, which was followed by a Na+-free solution in both the bath and lumen. The rate of pHi recovery after re-addition of Na+ to the luminal solution was calculated as a measure of the activity of the apical NHE. The rate of pHi recovery was 0.12 ± 0.01 pH unit/min (mean ± SD, n = 8) in wild-type ducts which was completely inhibited by 100 μM HOE642, an inhibitor of NHE. Forskolin (1 μM) reduced the apical NHE activity to 0.05 ± 0.01 (n = 9, p <0.01). The apical NHE activity in CF (δF/δF) ducts was 0.20 ± 0.01 (n = 6), which was significantly (p < 0.01) higher than that in wild-type ducts and was further accelerated to 0.66 ± 0.11 (n = 6, p < 0.01) by forskolin. Under normal conditions, the apical NHE activity in mouse pancreatic duct cells is inhibited by cAMP via CFTR-dependent mechanisms. In the absence of functional CFTR, the apical NHE activity is stimulated by cAMP, which may be responsible for reduced HCO3− secretion in CF. [J Physiol Sci. 2007;57 Suppl:S45]
