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cAMP activation of CF-affected Cl? conductance in both cell membranes of an absorptive epithelium
- Source :
- The Journal of Membrane Biology. 130
- Publication Year :
- 1992
- Publisher :
- Springer Science and Business Media LLC, 1992.
-
Abstract
- Cystic fibrosis (CF) is characterized by abnormal epithelial Cl- conductance (GCl). In vitro studies that have shown that cAMP regulation is an intrinsic property of the CF-affected GCl(CF-GCl) have been carried out previously on cultured secretory cells and on nonepithelial cells. Even though GCl in absorption is defective in CF, a clear demonstration of cAMP regulation of CF-GCl in a purely absorptive tissue is lacking. We studied the cAMP regulation of CF-GCl in the microperfused intact human reabsorptive sweat duct. About 40% of the ducts responded to cAMP (responsive) while the remainder of the ducts did not. In responsive ducts, cAMP-elevating agents: beta-adrenergic agonist isoproterenol (IPR), CPT-cAMP, forskolin, theophylline or IBMX increased Gt by about 2.3-fold (n = no. of ducts = 8). Removal of media Cl-, but not amiloride pretreatment (in the lumen), abolished the cAMP response, indicating exclusive activation of GCl. cAMP activated both apical and basolateral GCl. cAMP hyperpolarized gluconate: Cl- (lumen:bath) transepithelial bionic potentials (delta Vt = -20.3 +/- 5.2 mV, mean +/- SE, n = 9) and transepithelial 3: 1 luminal NaCl dilution diffusion potentials (delta Vt = -8.8 +/- 2.9 mV, n = 5). cAMP activated basolateral GCl as indicated by increased bi-ionic (gluconate:Cl-, bath:lumen) diffusion potentials (by about 12 mV). The voltage divider ratio in symmetric NaCl solutions increased by 60%. Compared to responsive ducts, nonresponsive ducts were characterized by smaller spontaneous transepithelial potentials in symmetrical Ringer's solution (Vt = -6.9 +/- 0.8 mV, n = 24, nonresponsive vs. -19.4 +/- 1.8 mV, n = 22, responsive ducts) but larger bi-ionic potentials (-94 +/- 6 mV, n = 35, nonresponsive vs. -65 +/- 5 mV, n = 17, responsive ducts) and dilution diffusion potentials (-40 +/- 5 mV, n = 11, nonresponsive vs. -29 +/- 3 mV, n = 7, responsive ducts). These results are consistent with an inherently (prestimulus) maximal activation of GCl in nonresponsive ducts and submaximal activation of GCl in responsive ducts. We conclude that cAMP activates CF-GCl which is expressed and abnormal in both apical and basal membranes of this absorptive epithelium in CF.
- Subjects :
- Adult
Intracellular Fluid
Male
Agonist
medicine.medical_specialty
IBMX
Cystic Fibrosis
Physiology
medicine.drug_class
Skin Absorption
Biophysics
Lumen (anatomy)
Dinoprostone
Epithelium
Ion Channels
Membrane Potentials
Diffusion
chemistry.chemical_compound
Chlorides
Internal medicine
Cyclic AMP
medicine
Humans
Theophylline
Membrane potential
Forskolin
Electric Conductivity
Epithelial Cells
Cell Biology
Adrenergic beta-Agonists
Sweat Glands
Amiloride
medicine.anatomical_structure
Endocrinology
Parasympathomimetics
chemistry
medicine.drug
Subjects
Details
- ISSN :
- 14321424 and 00222631
- Volume :
- 130
- Database :
- OpenAIRE
- Journal :
- The Journal of Membrane Biology
- Accession number :
- edsair.doi.dedup.....abdc2daa33f34a12335b065ae228b90f