Document Detail

Effects of methacholine and uridine 5'-triphosphate on tracheal mucus rheology in mice.
MedLine Citation:
PMID:  10696075     Owner:  NLM     Status:  MEDLINE    
We compared the action of methacholine (MCh) and uridine 5'-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 microl of 10(-2) M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (-21.3+/-2.0 mV MCh versus -14.1+/-1.6 mV control; -25.4+/-2.5 mV UTP versus -19.2+/-1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from -15.2+/-2.9 to -12.0+/-2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54+/-0.09 versus 2.99+/-0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 +/-0.10 versus 2.57+/-0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19+/-0.09 mg/h, whereas after MCh stimulation, it increased to 2.83+/-0.78 mg/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL/6 mice is less vigorous than with MCh, reflecting the limited population of Ca(2+)-dependent Cl(-) channels stimulated by UTP P(2) receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels.
E Sudo; M M Lee; W A Boyd; M King
Related Documents :
24881885 - Role of the mitochondrial ca(2+) uniporter in pb(2+)-induced oxidative stress in human ...
9950775 - Airway surface fluid volume and cl content in cystic fibrosis and normal bronchial xeno...
8823295 - A delta f508 mutation in mouse cystic fibrosis transmembrane conductance regulator resu...
17102035 - Discovering the mechanism of capacitative calcium entry.
9681185 - Thapsigargin and receptor-mediated activation of drosophila trpl channels stably expres...
8154765 - Tetanus toxin and clostridium perfringens enterotoxin as tools for the study of exocyto...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  22     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-14     Completed Date:  2000-04-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  373-9     Citation Subset:  IM    
Pulmonary Research Group, University of Alberta, Edmonton, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
Bronchoconstrictor Agents / pharmacology*
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
Epithelial Cells / chemistry,  drug effects,  secretion
Methacholine Chloride / pharmacology*
Mice, Inbred C57BL
Mucus / secretion*
Trachea / drug effects*,  secretion
Uridine Triphosphate / pharmacology*
Reg. No./Substance:
0/Bronchoconstrictor Agents; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 62-51-1/Methacholine Chloride; 63-39-8/Uridine Triphosphate

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

Previous Document:  Aquaporin-5 expression, but not other peripheral lung marker genes, is reduced in PTH/PTHrP receptor...
Next Document:  Pulmonary surfactant metabolism in infants lacking surfactant protein B.