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Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction

Item Type:Article
Title:Calcium-sensing receptor abrogates secretagogue- induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction
Creators Name:Geibel, J. and Sritharan, K. and Geibel, R. and Geibel, P. and Persing, J.S. and Seeger, A. and Roepke, T.K. and Deichstetter, M. and Prinz, C. and Cheng, S.X. and Martin, D. and Hebert, S.C.
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.
Keywords:Cholera, Diarrhea, Forskolin, STa Toxin, Quanylin, Animals, Knockout Mice , Mice, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:103
Number:25
Page Range:9390-9397
Date:20 June 2006
Official Publication:https://doi.org/10.1073/pnas.0602996103
PubMed:View item in PubMed

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