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Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 1999 Jan; Vol. 29 (1), pp. 5-13. - Publication Year :
- 1999
-
Abstract
- Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were -2.2 +/- 0.3 mV (lumen negative), 40.7 +/- 7.8 microA/cm2, and 66.5 +/- 9.6 Omega. cm2, respectively (n = 14). The addition of forskolin (10(-5) mol/L) to the apical and basolateral baths and that of adenosine 5'-triphosphate (ATP) (10(-4) mol/L) to the apical bath induced significant increases in Isc by 8.0 +/- 1.4 and 10.3 +/- 1.8 microA/cm2, respectively. Depletion of bathing solutions in Cl- and HCO3- significantly reduced baseline Isc and the forskolin- and ATP-induced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca2+/calmodulin-dependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P <.05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y2 purinoceptors and a calcium-dependent pathway.
- Subjects :
- Adenosine Triphosphate physiology
Adolescent
Adult
Anions metabolism
Biological Transport
Chloride Channels metabolism
Cyclic AMP physiology
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Electrophysiology
Extracellular Space metabolism
Female
Humans
In Vitro Techniques
Male
Mucous Membrane metabolism
Receptors, Purinergic P2 metabolism
Receptors, Purinergic P2Y2
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction physiology
Cystic Fibrosis metabolism
Gallbladder metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0270-9139
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 9862842
- Full Text :
- https://doi.org/10.1002/hep.510290142