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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Geibel, Peter Geibel, Rainer Roepke, Torsten K. Prinz, Christian Martin, David Seeger, Achim Hebert, Steven C. Geibel, John Sritharan, Kumudesh Cheng, Sam X. Deichstetter, Markus Persing, J. Scott |
| Description | Author Affiliation: Geibel J ( Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. john.geibel@yale.edu); |
| Abstract | The calcium-sensing receptor (CaSR) provides a fundamental mechanism for diverse cells to detect and respond to modulations in the ionic and nutrient compositions of their extracellular milieu. The roles for this receptor are largely unknown in the intestinal tract, where epithelial cells are normally exposed to large variations in extracellular solutes. Here, we show that colonic CaSR signaling stimulates the degradation of cyclic nucleotides by phosphodiesterases and describe the ability of receptor activation to reverse the fluid and electrolyte secretory actions of cAMP- and cGMP-generating secretagogues, including cholera toxin and heat stable Escherichia coli enterotoxin STa. Our results suggest a paradigm for regulation of intestinal fluid transport where fine tuning is accomplished by the counterbalancing effects of solute activation of the CaSR on neuronal and hormonal secretagogue actions. The reversal of cholera toxin- and STa endotoxin-induced fluid secretion by a small-molecule CaSR agonist suggests that these compounds may provide a unique therapy for secretory diarrheas. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Intestinal Secretions Metabolism Nucleotides, Cyclic Receptors, Calcium-Sensing Aniline Compounds Pharmacology Animals Bacterial Toxins Calcium Chemistry Cations, Divalent Drug Effects Mice Mice, Knockout Phenethylamines Phosphoric Diester Hydrolases Propylamines Agonists Genetics Type C Phospholipases Antagonists & Inhibitors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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