Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis
C Jiang, WE Finkbeiner, JH Widdicombe… - The Journal of …, 1997 - Wiley Online Library
C Jiang, WE Finkbeiner, JH Widdicombe, SS Miller
The Journal of physiology, 1997•Wiley Online Library1 There is evidence that defective submucosal gland secretion contributes to the airway
pathology of cystic fibrosis (CF). Using a capacitance probe technique, we have compared
fluid transport across submucosal gland cultures from individuals with and without CF. 2
Under baseline conditions,∼ 60% of non‐CF cultures secreted fluid; the rest absorbed. In
secreting tissues, amiloride increased secretion, whereas in absorbing tissues it reduced or
reversed absorption. 5‐Mtro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB) a blocker of the …
pathology of cystic fibrosis (CF). Using a capacitance probe technique, we have compared
fluid transport across submucosal gland cultures from individuals with and without CF. 2
Under baseline conditions,∼ 60% of non‐CF cultures secreted fluid; the rest absorbed. In
secreting tissues, amiloride increased secretion, whereas in absorbing tissues it reduced or
reversed absorption. 5‐Mtro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB) a blocker of the …
- 1There is evidence that defective submucosal gland secretion contributes to the airway pathology of cystic fibrosis (CF). Using a capacitance probe technique, we have compared fluid transport across submucosal gland cultures from individuals with and without CF.
- 2Under baseline conditions, ∼60% of non‐CF cultures secreted fluid; the rest absorbed. In secreting tissues, amiloride increased secretion, whereas in absorbing tissues it reduced or reversed absorption. 5‐Mtro‐2‐(3‐ phenylpropylamino)‐benzoate (NPPB) a blocker of the CF transmembrane conductance regulator (CFTR), converted secretion to absorption. Thus, the direction and magnitude of baseline fluid movement depended on a balance between active absorption of Na+ and cAMP‐dependent secretion of CI−.
- 38‐(4‐Chlorophenylthio)‐adenosine 3',5'‐cyclic monophosphate (CPT‐cAMP), methacholine and luminal uridine 5'‐triphosphate (UTP) all induced or increased fluid secretion across non‐CF cultures. Results with NPPB and with 4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonate (DIDS), a blocker of Ca2+ ‐activated CI− channels, suggested that fluid secretion induced by CPT‐cAMP was mediated primarily by CFTR; UTP acted entirely via Ca2+ ‐activated CI− channels, and methacholine activated both pathways.
- 4All CF cultures showed baseline fluid absorption, which was abolished by amiloride.
- 5CF cultures showed a normal secretory response to UTP, a reduced response to methacholine, and no response to CPT‐cAMP.
- 6Thus, the absorptive processes of airway glands are retained in CF, but the cAMP‐dependent secretory process is lost. This would markedly reduce the water content of gland secretions. The resulting change in viscosity would contribute to the accumulation of airway mucus which is characteristic of this disease.
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