Document Detail


Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates.
MedLine Citation:
PMID:  11694445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5'-triphosphate (UTP) approximately equal to adenosine 5'-triphosphate (ATP) approximately equal to ATP-gamma-S > uridine 5'-diphosphate approximately equal to adenosine 5'-diphosphate > alpha,beta-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/ phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.
Authors:
Y Chen; Y H Zhao; R Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  25     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-11-05     Completed Date:  2001-12-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  409-17     Citation Subset:  IM    
Affiliation:
Center for Comparative Respiratory Biology and Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism,  pharmacology
Animals
Cell Differentiation
Cells, Cultured
Enzyme Inhibitors / pharmacology
Estrenes / pharmacology
Female
Gene Expression Regulation
Humans
Intubation, Intratracheal
MAP Kinase Signaling System / drug effects
Mice
Mice, Inbred BALB C
Mucin 5AC
Mucin-5B
Mucins / drug effects,  genetics*,  secretion*
Naphthalenes / pharmacology
Protein Kinase C / antagonists & inhibitors
Pyrrolidinones / pharmacology
Respiratory Mucosa / cytology*,  physiology*
Signal Transduction*
Up-Regulation
Uridine Triphosphate / metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
ES 05707/ES/NIEHS NIH HHS; ES 06230/ES/NIEHS NIH HHS; ES 97030/ES/NIEHS NIH HHS; HL 35635/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Estrenes; 0/MUC5AC protein, human; 0/MUC5B protein, human; 0/Muc5ac protein, mouse; 0/Mucin 5AC; 0/Mucin-5B; 0/Mucins; 0/Naphthalenes; 0/Pyrrolidinones; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 121263-19-2/calphostin C; 142878-12-4/U 73343; 56-65-5/Adenosine Triphosphate; 63-39-8/Uridine Triphosphate; EC 2.7.11.13/Protein Kinase C
Comments/Corrections
Comment In:
Am J Respir Cell Mol Biol. 2001 Oct;25(4):397-400   [PMID:  11694442 ]

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