| Expression and regulation of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) in human colonic epithelial cells: role in the induction of cellular refractoriness to the heat-stable enterotoxin peptide. | |
| | |
MedLine Citation:
|
PMID: 10679826 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Stable toxin (ST) peptides are the causative agents for a severe form of watery diarrhea. These peptides bind to a membrane-associated form of guanylyl cyclase, guanylyl cyclase C. The result is an accumulation of cyclic guanosine monophosphate (cGMP) in the intestinal cell, regulating protein kinase activity and the phosphorylation of a number of proteins involved in ion transport across the intestine. Using the human T84 colonic cell line as a model system, we show that cGMP accumulation in these cells after ST application is regulated by the activity of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5). The presence of human PDE5 in this cell line was confirmed by Western blot analysis, using an antibody raised to the bovine enzyme, and by the observation that cGMP hydrolytic activity detected in T84 cell lysates was almost completely inhibited by low concentrations of zaprinast, a specific inhibitor of PDE5. An increase in activity of PDE5 was observed in T84 cell lysates on exposure to the ST peptide and prolonged exposure of T84 cells to the ST peptide led to the induction of cellular refractoriness in these cells, which was largely contributed in terms of an increased rate of degradation of cGMP in desensitized cells as a result of PDE5 activation. This activation was correlated with an increase in the affinity of the enzyme for the substrate cGMP, as well as an increased affinity for zaprinast. We provide evidence for the first time that cGMP levels in the human colonocyte are regulated by the cGMP-hydrolytic activity of PDE5 and suggest that the expression and regulation of PDE5 in the intestine could therefore be important in controlling cGMP-mediated signaling in this tissue. |
| | |
Authors:
|
M M Bakre; S Sopory; S S Visweswariah |
Related Documents
:
|
22436056 - Is impaired kupffer cell function really important to the pathogenesis of nonalcoholic ... 3734226 - Maintenance of whole cell isoproterenol and forskolin responsiveness in adenylate cycla... 1715816 - Cyclic amp-mediated modulation of immunoglobulin production in b cells by prostaglandin... 83946 - Effect of trh and dopamine on cyclic amp levels in enriched mammotroph and thyrotroph c... 20504066 - A combining method to enhance the in vitro differentiation of hepatic precursor cells. 6121926 - Thy-1 antigen on normal and neoplastic rat mammary tissues: changes in location and amo... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of cellular biochemistry Volume: 77 ISSN: 0730-2312 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2000 Feb |
Date Detail:
|
Created Date: 2000-03-24 Completed Date: 2000-03-24 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 159-67 Citation Subset: IM |
Copyright Information:
|
Copyright 2000 Wiley-Liss, Inc. |
Affiliation:
|
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
3',5'-Cyclic-GMP Phosphodiesterases
/
metabolism* Animals Bacterial Toxins / metabolism, toxicity* Cattle Cell Line Colon / metabolism*, pathology Cyclic GMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 5 Enterotoxins / metabolism, toxicity* Epithelial Cells / metabolism, pathology Humans Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
|
0/Bacterial Toxins; 0/Enterotoxins; 0/heat stable toxin (E coli); 7665-99-8/Cyclic GMP; EC 3.1.4.35/3',5'-Cyclic-GMP Phosphodiesterases; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 3.1.4.35/PDE5A protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Parathyroid hormone inhibits collagen synthesis and the activity of rat col1a1 transgenes mainly by ...
Next Document: A simplified urinary incontinence score for the evaluation of treatment outcomes.