Dual role of CFTR in cAMP-stimulated secretion across murine duodenum
LL Clarke, MC Harline - American Journal of Physiology …, 1998 - journals.physiology.org
LL Clarke, MC Harline
American Journal of Physiology-Gastrointestinal and Liver …, 1998•journals.physiology.orgThe role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-
stimulated HCO 3− secretion across the murine duodenum was investigated. Serosal-to-
mucosal flux of HCO 3−(J s→ m, in μeq⋅ cm− 2⋅ h− 1) and short-circuit current (I sc; in
μeq⋅ cm− 2⋅ h− 1) were measured by the pH stat method in duodenum from CFTR
knockout [CFTR (−)] and normal [CFTR (+)] mice. Under control conditions, forskolin
increased J s→ m and I sc (+ 1.7 and+ 3.5, respectively) across the CFTR (+) but not CFTR …
stimulated HCO 3− secretion across the murine duodenum was investigated. Serosal-to-
mucosal flux of HCO 3−(J s→ m, in μeq⋅ cm− 2⋅ h− 1) and short-circuit current (I sc; in
μeq⋅ cm− 2⋅ h− 1) were measured by the pH stat method in duodenum from CFTR
knockout [CFTR (−)] and normal [CFTR (+)] mice. Under control conditions, forskolin
increased J s→ m and I sc (+ 1.7 and+ 3.5, respectively) across the CFTR (+) but not CFTR …
The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated secretion across the murine duodenum was investigated. Serosal-to-mucosal flux of (J s→m, in μeq ⋅ cm−2 ⋅ h−1) and short-circuit current (I sc; in μeq ⋅ cm−2 ⋅ h−1) were measured by the pH stat method in duodenum from CFTR knockout [CFTR(−)] and normal [CFTR(+)] mice. Under control conditions, forskolin increased J s→m andI sc (+1.7 and +3.5, respectively) across the CFTR(+) but not CFTR(−) duodenum. Both the forskolin-stimulated ΔJ s→m and ΔI sc were abolished by the CFTR channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate, whereas inhibition of luminal Cl−/ exchange by luminal Cl− removal or DIDS reduced theJ s→m by ∼18% without a consistent effect on the ΔI sc. Methazolamide also reduced theJ s→m by 39% but did not affect the ΔI sc. When carbonic anhydrase-dependent secretion was isolated by using a CO2-gassed, -free Ringer bath, forskolin stimulated the J s→m andI sc (+0.7 and +2.0, respectively) across CFTR(+) but not CFTR(−) duodenum. Under these conditions, luminal Cl− substitution or DIDS abolished theJ s→m but not the ΔI sc. It was concluded that cAMP-stimulated secretion across the duodenum involves 1) electrogenic secretion via a CFTR conductance and2) electroneutral secretion via a CFTR-dependent Cl−/ exchange process that is closely associated with the carbonic anhydrase activity of the epithelium.
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