Document Detail

Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide.
MedLine Citation:
PMID:  12181176     Owner:  NLM     Status:  MEDLINE    
The present studies were undertaken to determine the direct effects of nitric oxide (NO) released from an exogenous donor, S-nitroso-N-acetyl pencillamine (SNAP) on Cl-/OH- exchange activity in human Caco-2 cells. Our results demonstrate that NO inhibits Cl-/OH- exchange activity in Caco-2 cells via cGMP-dependent protein kinases G (PKG) and C (PKC) signal-transduction pathways. Our data in support of this conclusion can be outlined as follows: 1) incubation of Caco-2 cells with SNAP (500 microM) for 30 min resulted in approximately 50% inhibition of DIDS-sensitive 36Cl uptake; 2) soluble guanylate cyclase inhibitors Ly-83583 and (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one significantly blocked the inhibition of Cl-/OH- exchange activity by SNAP; 3) addition of 8-bromo-cGMP (8-BrcGMP) mimicked the effects of SNAP; 4) specific PKG inhibitor KT-5823 significantly inhibited the decrease in Cl-/OH- exchange activity in response to either SNAP or 8-BrcGMP; 5) Cl-/OH-exchange activity in Caco-2 cells in response to SNAP was not altered in the presence of protein kinase A (PKA) inhibitor (Rp-cAMPS), demonstrating that the PKA pathway was not involved; 6) the effect of NO on Cl-/OH- exchange activity was mediated by PKC, because each of the two PKC inhibitors chelerythrine chloride and calphostin C blocked the SNAP-mediated inhibition of Cl-/OH- exchange activity; 7) SO/OH- exchange in Caco-2 cells was unaffected by SNAP. Our results suggest that NO-induced inhibition of Cl-/OH- exchange may play an important role in the pathophysiology of diarrhea associated with inflammatory bowel diseases.
Seema Saksena; Ravinder K Gill; Irfan A Syed; Sangeeta Tyagi; Waddah A Alrefai; K Ramaswamy; Pradeep K Dudeja
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  283     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-15     Completed Date:  2002-09-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G626-33     Citation Subset:  IM    
Section of Digestive and Liver Diseases, Department of Medicine, University of Illinois at Chicago and Chicago Veteran's Affairs System: West Side Division, Chicago, Illinois 60612, USA.
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MeSH Terms
Antiporters / antagonists & inhibitors,  metabolism*
Caco-2 Cells
Cyclic AMP / analogs & derivatives*,  pharmacology
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Cyclic GMP / physiology
Cyclic GMP-Dependent Protein Kinases / physiology
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
Nitric Oxide / physiology*
Nitric Oxide Donors / pharmacology
S-Nitroso-N-Acetylpenicillamine / pharmacology
Thionucleotides / pharmacology
Grant Support
Reg. No./Substance:
0/Antiporters; 0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/Thionucleotides; 0/chloride-base exchanger; 10102-43-9/Nitric Oxide; 23645-17-2/adenosine-3',5'-cyclic phosphorothioate; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 79032-48-7/S-Nitroso-N-Acetylpenicillamine; EC AMP-Dependent Protein Kinases; EC GMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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