Eintrag weiter verarbeiten
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes
Gespeichert in:
| Zeitschriftentitel: | The Journal of Physiology |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | The Journal of Physiology, 581, 2007, 3, S. 1235-1246 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula |
|---|---|
| author |
Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula |
| spellingShingle |
Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula The Journal of Physiology NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes Physiology |
| author_sort |
cinar, ayhan |
| spelling |
Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula 0022-3751 1469-7793 Wiley Physiology http://dx.doi.org/10.1113/jphysiol.2007.131722 <jats:p>The PDZ‐binding protein PDZK1 (NHERF3/CAP70/PDZ‐dc‐1) <jats:italic>in vitro</jats:italic> binds to NHE3, but its role in the regulation of NHE3 activity in native enterocytes is unknown. This study was undertaken to understand the physiological role of PDZK1 in regulating NHE3 activity in native murine colonic enterocytes. NHE3 transport rates were assessed fluorometrically in BCECF‐loaded colonic crypts in the NHE3‐expressing cryptal openings by measuring acid‐activated, Na<jats:sup>+</jats:sup>‐dependent, Hoe 642‐insensitive proton efflux rates. NHE3 mRNA expression levels and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative PCR and Western analysis and immunohistochemistry. In <jats:italic>pdzk1</jats:italic>−/− colonic surface cells, acid‐activated NHE3 transport rates were strongly reduced, and the inhibitory effect of forskolin and ionomcyin was virtually abolished. Hyperosmolarity, on the other hand, still had an inhibitory effect. In addition, the NHE3‐selective inhibitor S1611 inhibited acid‐activated NHE3 activity in <jats:italic>pdzk1</jats:italic>−/− and +/+ mice, suggesting that functional NHE3 is present in <jats:italic>pdzk1</jats:italic>‐deficient colonocytes. NHE1 and NHE2 activity was not altered in <jats:italic>pdzk1</jats:italic>−/− colonic crypts. Immunohistochemistry revealed apical NHE3 staining in <jats:italic>pdzk1</jats:italic>−/− and +/+ proximal colon, and Western blot analysis revealed no difference in NHE3 abundance in colonic enterocyte homogenate as well as brush border membrane. Lack of the PDZ‐adaptor protein PDZK1 in murine proximal colonic enterocytes does not influence NHE3 abundance or targeting to the apical membrane, but abolishes NHE3 regulation by cAMPergic and Ca<jats:sup>2+</jats:sup> ‐dependent pathways. It leaves NHE3 inhibition by hyperosmolarity intact, suggesting an important and selective role for PDZK1 in the agonist‐mediated regulation of intestinal NHE3 activity.</jats:p> NHE3 inhibition by cAMP and Ca<sup>2+</sup> is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes The Journal of Physiology |
| doi_str_mv |
10.1113/jphysiol.2007.131722 |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDA3LjEzMTcyMg |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDA3LjEzMTcyMg |
| institution |
DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 |
| imprint |
Wiley, 2007 |
| imprint_str_mv |
Wiley, 2007 |
| issn |
0022-3751 1469-7793 |
| issn_str_mv |
0022-3751 1469-7793 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
cinar2007nhe3inhibitionbycampandca2isabolishedinpdzdomainproteinpdzk1deficientmurineenterocytes |
| publishDateSort |
2007 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Physiology |
| source_id |
49 |
| title |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_unstemmed |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_full |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_fullStr |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_full_unstemmed |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_short |
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_sort |
nhe3 inhibition by camp and ca<sup>2+</sup> is abolished in pdz‐domain protein pdzk1‐deficient murine enterocytes |
| topic |
Physiology |
| url |
http://dx.doi.org/10.1113/jphysiol.2007.131722 |
| publishDate |
2007 |
| physical |
1235-1246 |
| description |
<jats:p>The PDZ‐binding protein PDZK1 (NHERF3/CAP70/PDZ‐dc‐1) <jats:italic>in vitro</jats:italic> binds to NHE3, but its role in the regulation of NHE3 activity in native enterocytes is unknown. This study was undertaken to understand the physiological role of PDZK1 in regulating NHE3 activity in native murine colonic enterocytes. NHE3 transport rates were assessed fluorometrically in BCECF‐loaded colonic crypts in the NHE3‐expressing cryptal openings by measuring acid‐activated, Na<jats:sup>+</jats:sup>‐dependent, Hoe 642‐insensitive proton efflux rates. NHE3 mRNA expression levels and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative PCR and Western analysis and immunohistochemistry. In <jats:italic>pdzk1</jats:italic>−/− colonic surface cells, acid‐activated NHE3 transport rates were strongly reduced, and the inhibitory effect of forskolin and ionomcyin was virtually abolished. Hyperosmolarity, on the other hand, still had an inhibitory effect. In addition, the NHE3‐selective inhibitor S1611 inhibited acid‐activated NHE3 activity in <jats:italic>pdzk1</jats:italic>−/− and +/+ mice, suggesting that functional NHE3 is present in <jats:italic>pdzk1</jats:italic>‐deficient colonocytes. NHE1 and NHE2 activity was not altered in <jats:italic>pdzk1</jats:italic>−/− colonic crypts. Immunohistochemistry revealed apical NHE3 staining in <jats:italic>pdzk1</jats:italic>−/− and +/+ proximal colon, and Western blot analysis revealed no difference in NHE3 abundance in colonic enterocyte homogenate as well as brush border membrane. Lack of the PDZ‐adaptor protein PDZK1 in murine proximal colonic enterocytes does not influence NHE3 abundance or targeting to the apical membrane, but abolishes NHE3 regulation by cAMPergic and Ca<jats:sup>2+</jats:sup> ‐dependent pathways. It leaves NHE3 inhibition by hyperosmolarity intact, suggesting an important and selective role for PDZK1 in the agonist‐mediated regulation of intestinal NHE3 activity.</jats:p> |
| container_issue |
3 |
| container_start_page |
1235 |
| container_title |
The Journal of Physiology |
| container_volume |
581 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792347428885626887 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T17:55:07.76Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=NHE3+inhibition+by+cAMP+and+Ca2%2B+is+abolished+in+PDZ%E2%80%90domain+protein+PDZK1%E2%80%90deficient+murine+enterocytes&rft.date=2007-06-15&genre=article&issn=1469-7793&volume=581&issue=3&spage=1235&epage=1246&pages=1235-1246&jtitle=The+Journal+of+Physiology&atitle=NHE3+inhibition+by+cAMP+and+Ca%3Csup%3E2%2B%3C%2Fsup%3E+is+abolished+in+PDZ%E2%80%90domain+protein+PDZK1%E2%80%90deficient+murine+enterocytes&aulast=Seidler&aufirst=Ursula&rft_id=info%3Adoi%2F10.1113%2Fjphysiol.2007.131722&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792347428885626887 |
| author | Cinar, Ayhan, Chen, Mingmin, Riederer, Brigitte, Bachmann, Oliver, Wiemann, Martin, Manns, Michael, Kocher, Olivier, Seidler, Ursula |
| author_facet | Cinar, Ayhan, Chen, Mingmin, Riederer, Brigitte, Bachmann, Oliver, Wiemann, Martin, Manns, Michael, Kocher, Olivier, Seidler, Ursula, Cinar, Ayhan, Chen, Mingmin, Riederer, Brigitte, Bachmann, Oliver, Wiemann, Martin, Manns, Michael, Kocher, Olivier, Seidler, Ursula |
| author_sort | cinar, ayhan |
| container_issue | 3 |
| container_start_page | 1235 |
| container_title | The Journal of Physiology |
| container_volume | 581 |
| description | <jats:p>The PDZ‐binding protein PDZK1 (NHERF3/CAP70/PDZ‐dc‐1) <jats:italic>in vitro</jats:italic> binds to NHE3, but its role in the regulation of NHE3 activity in native enterocytes is unknown. This study was undertaken to understand the physiological role of PDZK1 in regulating NHE3 activity in native murine colonic enterocytes. NHE3 transport rates were assessed fluorometrically in BCECF‐loaded colonic crypts in the NHE3‐expressing cryptal openings by measuring acid‐activated, Na<jats:sup>+</jats:sup>‐dependent, Hoe 642‐insensitive proton efflux rates. NHE3 mRNA expression levels and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative PCR and Western analysis and immunohistochemistry. In <jats:italic>pdzk1</jats:italic>−/− colonic surface cells, acid‐activated NHE3 transport rates were strongly reduced, and the inhibitory effect of forskolin and ionomcyin was virtually abolished. Hyperosmolarity, on the other hand, still had an inhibitory effect. In addition, the NHE3‐selective inhibitor S1611 inhibited acid‐activated NHE3 activity in <jats:italic>pdzk1</jats:italic>−/− and +/+ mice, suggesting that functional NHE3 is present in <jats:italic>pdzk1</jats:italic>‐deficient colonocytes. NHE1 and NHE2 activity was not altered in <jats:italic>pdzk1</jats:italic>−/− colonic crypts. Immunohistochemistry revealed apical NHE3 staining in <jats:italic>pdzk1</jats:italic>−/− and +/+ proximal colon, and Western blot analysis revealed no difference in NHE3 abundance in colonic enterocyte homogenate as well as brush border membrane. Lack of the PDZ‐adaptor protein PDZK1 in murine proximal colonic enterocytes does not influence NHE3 abundance or targeting to the apical membrane, but abolishes NHE3 regulation by cAMPergic and Ca<jats:sup>2+</jats:sup> ‐dependent pathways. It leaves NHE3 inhibition by hyperosmolarity intact, suggesting an important and selective role for PDZK1 in the agonist‐mediated regulation of intestinal NHE3 activity.</jats:p> |
| doi_str_mv | 10.1113/jphysiol.2007.131722 |
| facet_avail | Online, Free |
| finc_class_facet | Biologie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDA3LjEzMTcyMg |
| imprint | Wiley, 2007 |
| imprint_str_mv | Wiley, 2007 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
| issn | 0022-3751, 1469-7793 |
| issn_str_mv | 0022-3751, 1469-7793 |
| language | English |
| last_indexed | 2024-03-01T17:55:07.76Z |
| match_str | cinar2007nhe3inhibitionbycampandca2isabolishedinpdzdomainproteinpdzk1deficientmurineenterocytes |
| mega_collection | Wiley (CrossRef) |
| physical | 1235-1246 |
| publishDate | 2007 |
| publishDateSort | 2007 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Physiology |
| source_id | 49 |
| spelling | Cinar, Ayhan Chen, Mingmin Riederer, Brigitte Bachmann, Oliver Wiemann, Martin Manns, Michael Kocher, Olivier Seidler, Ursula 0022-3751 1469-7793 Wiley Physiology http://dx.doi.org/10.1113/jphysiol.2007.131722 <jats:p>The PDZ‐binding protein PDZK1 (NHERF3/CAP70/PDZ‐dc‐1) <jats:italic>in vitro</jats:italic> binds to NHE3, but its role in the regulation of NHE3 activity in native enterocytes is unknown. This study was undertaken to understand the physiological role of PDZK1 in regulating NHE3 activity in native murine colonic enterocytes. NHE3 transport rates were assessed fluorometrically in BCECF‐loaded colonic crypts in the NHE3‐expressing cryptal openings by measuring acid‐activated, Na<jats:sup>+</jats:sup>‐dependent, Hoe 642‐insensitive proton efflux rates. NHE3 mRNA expression levels and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative PCR and Western analysis and immunohistochemistry. In <jats:italic>pdzk1</jats:italic>−/− colonic surface cells, acid‐activated NHE3 transport rates were strongly reduced, and the inhibitory effect of forskolin and ionomcyin was virtually abolished. Hyperosmolarity, on the other hand, still had an inhibitory effect. In addition, the NHE3‐selective inhibitor S1611 inhibited acid‐activated NHE3 activity in <jats:italic>pdzk1</jats:italic>−/− and +/+ mice, suggesting that functional NHE3 is present in <jats:italic>pdzk1</jats:italic>‐deficient colonocytes. NHE1 and NHE2 activity was not altered in <jats:italic>pdzk1</jats:italic>−/− colonic crypts. Immunohistochemistry revealed apical NHE3 staining in <jats:italic>pdzk1</jats:italic>−/− and +/+ proximal colon, and Western blot analysis revealed no difference in NHE3 abundance in colonic enterocyte homogenate as well as brush border membrane. Lack of the PDZ‐adaptor protein PDZK1 in murine proximal colonic enterocytes does not influence NHE3 abundance or targeting to the apical membrane, but abolishes NHE3 regulation by cAMPergic and Ca<jats:sup>2+</jats:sup> ‐dependent pathways. It leaves NHE3 inhibition by hyperosmolarity intact, suggesting an important and selective role for PDZK1 in the agonist‐mediated regulation of intestinal NHE3 activity.</jats:p> NHE3 inhibition by cAMP and Ca<sup>2+</sup> is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes The Journal of Physiology |
| spellingShingle | Cinar, Ayhan, Chen, Mingmin, Riederer, Brigitte, Bachmann, Oliver, Wiemann, Martin, Manns, Michael, Kocher, Olivier, Seidler, Ursula, The Journal of Physiology, NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes, Physiology |
| title | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_full | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_fullStr | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_full_unstemmed | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_short | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| title_sort | nhe3 inhibition by camp and ca<sup>2+</sup> is abolished in pdz‐domain protein pdzk1‐deficient murine enterocytes |
| title_unstemmed | NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes |
| topic | Physiology |
| url | http://dx.doi.org/10.1113/jphysiol.2007.131722 |