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
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 s...
Published in: | Journal of Clinical Investigation |
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Language: | English |
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American Society for Clinical Investigation
1998
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Online Access: | http://edoc.mdc-berlin.de/5681/ https://edoc.mdc-berlin.de/5681/ http://edoc.mdc-berlin.de/5681/1/5681oa.pdf https://doi.org/10.1172/JCI803 |
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ftmdcberlin:oai:edoc.mdc-berlin.de:5681 2023-05-15T18:51:08+02:00 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 Lehrich, R.W. Aller, S.G. Webster, P. Marino, C.R. Forrest, J.N. .J.r. 1998-02-15 application/pdf http://edoc.mdc-berlin.de/5681/ https://edoc.mdc-berlin.de/5681/ http://edoc.mdc-berlin.de/5681/1/5681oa.pdf https://doi.org/10.1172/JCI803 en eng American Society for Clinical Investigation http://edoc.mdc-berlin.de/5681/1/5681oa.pdf 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. Lehrich, R.W. and Aller, S.G. and Webster, P. and Marino, C.R. and Forrest, J.N. .J.r. Journal of Clinical Investigation 101 (4): 737-745. 15 February 1998 Cardiovascular and Metabolic Diseases Article PeerReviewed 1998 ftmdcberlin https://doi.org/10.1172/JCI803 2022-01-01T19:06:59Z 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. Article in Journal/Newspaper spiny dogfish Squalus acanthias Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository Journal of Clinical Investigation 101 4 737 745 |
institution |
Open Polar |
collection |
Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
op_collection_id |
ftmdcberlin |
language |
English |
topic |
Cardiovascular and Metabolic Diseases |
spellingShingle |
Cardiovascular and Metabolic Diseases Lehrich, R.W. Aller, S.G. Webster, P. Marino, C.R. Forrest, J.N. .J.r. 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 |
topic_facet |
Cardiovascular and Metabolic Diseases |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Lehrich, R.W. Aller, S.G. Webster, P. Marino, C.R. Forrest, J.N. .J.r. |
author_facet |
Lehrich, R.W. Aller, S.G. Webster, P. Marino, C.R. Forrest, J.N. .J.r. |
author_sort |
Lehrich, R.W. |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
American Society for Clinical Investigation |
publishDate |
1998 |
url |
http://edoc.mdc-berlin.de/5681/ https://edoc.mdc-berlin.de/5681/ http://edoc.mdc-berlin.de/5681/1/5681oa.pdf https://doi.org/10.1172/JCI803 |
genre |
spiny dogfish Squalus acanthias |
genre_facet |
spiny dogfish Squalus acanthias |
op_relation |
http://edoc.mdc-berlin.de/5681/1/5681oa.pdf 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. Lehrich, R.W. and Aller, S.G. and Webster, P. and Marino, C.R. and Forrest, J.N. .J.r. Journal of Clinical Investigation 101 (4): 737-745. 15 February 1998 |
op_doi |
https://doi.org/10.1172/JCI803 |
container_title |
Journal of Clinical Investigation |
container_volume |
101 |
container_issue |
4 |
container_start_page |
737 |
op_container_end_page |
745 |
_version_ |
1766244921551880192 |