Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis

C. Jiang, W. E. Finkbeiner, Jonathan Widdicombe, S. S. Miller

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

1. There is evidence that defective submucosal gland secretion contributes to the airway pathology of cystic fibrosis (CP). 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-Nitro-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 Cl-. 3. 8-(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 Cl- channels, suggested that fluid secretion induced by CPT-cAMP was mediated primarily by CFTR; UTP acted entirely via Ca2+-activated Cl- channels, and methacholine activated both pathways. 4. All CF cultures showed baseline fluid absorption, which was abolished by amiloride. 5. CF cultures showed a normal secretory response to UTP, a reduced response to methacholine, and no response to CPT-cAMP. 6. Thus, 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.

Original languageEnglish (US)
Pages (from-to)637-647
Number of pages11
JournalJournal of Physiology
Volume501
Issue number3
DOIs
StatePublished - Jun 15 1997
Externally publishedYes

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Cystic Fibrosis
Uridine Triphosphate
Methacholine Chloride
Fluids and Secretions
Amiloride
Benzoates
Secretory Pathway
Mucus
Viscosity
Cyclic AMP
Pathology
Water

ASJC Scopus subject areas

  • Physiology

Cite this

Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis. / Jiang, C.; Finkbeiner, W. E.; Widdicombe, Jonathan; Miller, S. S.

In: Journal of Physiology, Vol. 501, No. 3, 15.06.1997, p. 637-647.

Research output: Contribution to journalArticle

Jiang, C. ; Finkbeiner, W. E. ; Widdicombe, Jonathan ; Miller, S. S. / Fluid transport across cultures of human tracheal glands is altered in cystic fibrosis. In: Journal of Physiology. 1997 ; Vol. 501, No. 3. pp. 637-647.
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abstract = "1. There is evidence that defective submucosal gland secretion contributes to the airway pathology of cystic fibrosis (CP). 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-Nitro-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 Cl-. 3. 8-(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 Cl- channels, suggested that fluid secretion induced by CPT-cAMP was mediated primarily by CFTR; UTP acted entirely via Ca2+-activated Cl- channels, and methacholine activated both pathways. 4. All CF cultures showed baseline fluid absorption, which was abolished by amiloride. 5. CF cultures showed a normal secretory response to UTP, a reduced response to methacholine, and no response to CPT-cAMP. 6. Thus, 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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