Vasoactive intestinal peptide, forskolin, and genistein increase apical CFTR trafficking in the rectal gland of the spiny dogfish, Squalus acanthias. Acute regulation of CFTR trafficking in an intact epithelium
| Autor: | P Webster, John N. Forrest, C R Marino, Ruediger W. Lehrich, Stephen G. Aller |
|---|---|
| Přispěvatelé: | MDC Library |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Antimetabolites Vasoactive intestinal peptide Cystic Fibrosis Transmembrane Conductance Regulator 570 Life Sciences Biology Immunofluorescence Cystic fibrosis Antibodies 610 Medical Sciences Medicine Salt Gland Xenopus laevis chemistry.chemical_compound Fluorescence Microscopy Chlorides Internal medicine medicine Humans Animals Secretion Forskolin medicine.diagnostic_test Colforsin General Medicine Apical membrane medicine.disease Genistein Epithelium Cystic fibrosis transmembrane conductance regulator Cell biology Perfusion Endocrinology medicine.anatomical_structure Microscopy Fluorescence chemistry Cardiovascular and Metabolic Diseases Dogfish biology.protein Frogs Female Research Article Vasoactive Intestinal Peptide |
| Zdroj: | Journal of Clinical Investigation 101 (4): 737-745. |
| ISSN: | 0021-9738 |
| Popis: | Defective trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common cause of cystic fibrosis. In chloride-secreting epithelia, it is well established that CFTR localizes to intracellular organelles and to apical membranes. However, it is controversial whether secretagogues regulate the trafficking of CFTR. To investigate whether acute hormonal stimulation of chloride secretion is coupled to the trafficking of CFTR, we used the intact shark rectal gland, a model tissue in which salt secretion is dynamically regulated and both chloride secretion and cellular CFTR immunofluorescence can be quantified in parallel. In rectal glands perfused under basal conditions without secretagogues, Cl- secretion was 151+/-65 microeq/h/g. Vasoactive intestinal peptide (VIP), forskolin, and genistein led to 10-, 6-, and 4-fold increases in Cl- secretion. In basal glands, quantitative confocal microscopy revealed CFTR immunofluorescence extending from the apical membrane deeply into the cell (7.28+/-0.35 micron). During stimulation with secretagogues, apical extension of CFTR immunofluorescence into the cell was reduced significantly to 3.24+/-0.08 micron by VIP, 4.08+/-0.13 by forskolin, and 3.19+/-0.1 by genistein (P < 0.001). Moreover, the peak intensity of CFTR fluorescence shifted towards the apical membrane (peak fluorescence 2.5+/-0.13 micron basal vs. 1.51+/-0.06, 1.77+/-0.1, and 1.38+/-0.05 for VIP, forskolin, and genistein; all P < 0.001). The increase in both Cl- secretion and apical CFTR trafficking reversed to basal values after removal of VIP. These data provide the first quantitative morphological evidence for acute hormonal regulation of CFTR trafficking in an intact epithelial tissue. |
| Databáze: | OpenAIRE |
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