Peripheral Guanylate Cyclase‐C modulation of corticolimbic activation and corticotropin‐releasing factor signaling in a rat model of stress‐induced colonic hypersensitivity

2020 ◽  
Author(s):  
Casey O. Ligon ◽  
Gerhard Hannig ◽  
Beverley Greenwood‐Van Meerveld
Keyword(s):  
Guanylate Cyclase ◽  
Rat Model ◽  
Corticotropin Releasing Factor ◽  
Guanylate Cyclase C

scholarly journals Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Mitchell B. Cohen ◽  
Benjamin D. Gold ◽  
Stavra A. Xanthakos ◽  
Nicholas CaJacob ◽  
Taryn Weissman ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Guanylate Cyclase ◽  
Guanylate Cyclase C

scholarly journals Gastric corticotropin-releasing factor influences mast cell infiltration in a rat model of functional dyspepsia

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203704 ◽  
Author(s):  
Shin-ichiro Hagiwara ◽  
Esha Kaushal ◽  
Sreenivasan Paruthiyil ◽  
Pankaj J. Pasricha ◽  
Burcu Hasdemir ◽  
...  
Keyword(s):  
Mast Cell ◽  
Functional Dyspepsia ◽  
Rat Model ◽  
Corticotropin Releasing Factor ◽  
Cell Infiltration

Phase II Clinical Evaluation of SP-304, a Guanylate Cyclase-C Agonist, for Treatment of Chronic Constipation

2010 ◽  
Vol 105 ◽  
pp. S487-S488 ◽  
Author(s):  
Kunwar Shailubhai ◽  
Craig Talluto ◽  
Stephen Comiskey ◽  
John Foss ◽  
Alan Joslyn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Evaluation ◽  
Guanylate Cyclase ◽  
Chronic Constipation ◽  
Guanylate Cyclase C

A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion

2004 ◽  
Vol 286 (1) ◽  
pp. G95-G101 ◽  
Author(s):  
S. P. Rao ◽  
Z. Sellers ◽  
D. L. Crombie ◽  
D. L. Hogan ◽  
E. A. Mann ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Mek Inhibitor ◽  
Acid Exposure ◽  
Wild Type ◽  
Heat Stable ◽  
Guanylate Cyclase C ◽  
Perfusion Studies ◽  
Erk Phosphorylation

Luminal acidification provides the strongest physiological stimulus for duodenal [Formula: see text] secretion. Various neurohumoral mechanisms are believed to play a role in acid-stimulated [Formula: see text] secretion. Previous studies in the rat and human duodenum have shown that guanylin and Escherichia coli heat-stable toxin, both ligands of the transmembrane guanylyl cyclase receptor [guanylate cyclase C (GC-C)], are potent stimulators for duodenal [Formula: see text] secretion. We postulated that the GC-C receptor plays an important role in acid-stimulated [Formula: see text] secretion. In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal [Formula: see text] secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts. Pretreatment with PD-98059, an MEK inhibitor, resulted in attenuation of duodenal [Formula: see text] secretion in response to acid stimulation in the WT mice with no further effect in the KO mice. In vitro cGMP generation studies demonstrated a significant and comparable increase in cGMP levels on acid exposure in the duodenum of both WT and KO mice. In addition, a rapid, time-dependent phosphorylation of ERK was observed with acid exposure in the duodenum of WT mice, whereas a marked attenuation in ERK phosphorylation was observed in the KO animals despite equivalent levels of ERK in both groups of animals. On the basis of these studies, we conclude that transmembrane GC-C is a key mediator of acid-stimulated duodenal [Formula: see text] secretion. Furthermore, ERK phosphorylation may be an important intracellular mediator of duodenal [Formula: see text] secretion.

scholarly journals Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine

2017 ◽  
Vol 5 (11) ◽  
pp. e13299 ◽  
Author(s):  
Md. Kaimul Ahsan ◽  
Boris Tchernychev ◽  
Marco M. Kessler ◽  
Robert M. Solinga ◽  
David Arthur ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guanylate Cyclase ◽  
Guanylate Cyclase C ◽  
Protein Kinase Ii

scholarly journals Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intercellular paracrine signaling pathways

2001 ◽  
Vol 170 (1) ◽  
pp. 267-275 ◽  
Author(s):  
H Kulaksiz ◽  
Y Cetin
Keyword(s):  
Epithelial Cells ◽  
Guanylate Cyclase ◽  
Human Pancreas ◽  
Membrane Domain ◽  
Apical Cell Membrane ◽  
Ductal Cells ◽  
Pancreatic Ductal Cells ◽  
Cellular Expression ◽  
Guanylate Cyclase C ◽  
Electrolyte Secretion

The intestinal peptide hormone uroguanylin regulates electrolyte/fluid transport in the gastrointestinal epithelium by binding to its receptor, guanylate cyclase C (GC-C), and thus specifically coupling to activation of cystic fibrosis transmembrane conductance regulator (CFTR). Since CFTR is crucially involved in pancreatic electrolyte secretion, we investigated the human pancreas for expression and cell-specific localization of uroguanylin and guanylate cyclase C as potential regulatory components of pancreatic electrolyte secretion. RT-PCR analyses with specific primers revealed that uroguanylin and GC-C are expressed in the human pancreas (and in the duodenum, used as positive control); at the translational level, western blotting analyses with peptide- and region-specific antibodies identified the presence of 12.5 kDa uroguanylin and 130 kDa GC-C in both human pancreatic and intestinal extracts. At the cellular level, uroguanylin and GC-C immunoreactivities were absent from the islets of Langerhans but were exclusively confined to the exocrine parenchyma. Hence, uroguanylin was localized to the centroacinar cells typical of the pancreas, and also to epithelial cells of the intercalated, intralobular and interlobular ducts where the peptide was primarily concentrated adluminally to the apical portion of the respective cells. Coincidently, correlative studies localized the GC-C receptor to the epithelial cells of the ductal network, where it was confined exclusively to the apical cell membrane that evidently represents the functionally relevant target membrane domain for the regulatory peptide. In view of the fact that CFTR is highly expressed in pancreatic ductal cells where uroguanylin and its receptor are also localized, we assume that uroguanylin, an intrinsic pancreatic peptide, is involved in the regulation of electrolyte/water secretion in the ductal system via GC-C and CFTR. The particular cellular expression of uroguanylin in duct cells and the localization of GC-C to the duct cell apical membrane domain predict a novel route of intercellular signaling and luminal activation of GC-C via the pancreatic juice.

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