Document Detail


ATP secretion in the male reproductive tract: essential role of CFTR.
MedLine Citation:
PMID:  22711960     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Extracellular ATP is essential for the function of the epididymis and spermatozoa, but ATP release in the epididymis remains uncharacterized. We investigated here whether epithelial cells release ATP into the lumen of the epididymis, and we examined the role of the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) and HCO(3)(-) conducting ion channel known to be associated with male fertility, in this process. Immunofluorescence labelling of mouse cauda epididymidis showed expression of CFTR in principal cells but not in other epithelial cells. CFTR mRNA was not detectable in clear cells isolated by fluorescence-activated cell sorting (FACS) from B1-EGFP mice, which express enhanced green fluorescent protein (EGFP) exclusively in these cells in the epididymis. ATP release was detected from the mouse epididymal principal cell line (DC2) and increased by adrenaline and forskolin. Inhibition of CFTR with CFTR(inh172) and transfection with CFTR-specific siRNAs in DC2 cells reduced basal and forskolin-activated ATP release. CFTR-dependent ATP release was also observed in primary cultures of mouse epididymal epithelial cells. In addition, steady-state ATP release was detected in vivo in mice, by measuring ATP concentration in a solution perfused through the lumen of the cauda epididymidis tubule and collected by cannulation of the vas deferens. Luminal CFTR(inh172) reduced the ATP concentration detected in the perfusate. This study shows that CFTR is involved in the regulation of ATP release from principal cells in the cauda epididymidis. Given that mutations in CFTR are a leading cause of male infertility, we propose that defective ATP signalling in the epididymis might contribute to dysfunction of the male reproductive tract associated with these mutations.
Authors:
Ye Chun Ruan; Winnie W C Shum; Clémence Belleannée; Nicolas Da Silva; Sylvie Breton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-18
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2013-02-11     Revised Date:  2013-10-23    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  4209-22     Citation Subset:  IM    
Affiliation:
Center for Systems Biology/Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*
Animals
Base Sequence
Cell Line
Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors,  genetics,  metabolism*
Epididymis / cytology,  drug effects,  metabolism*
Epithelial Cells / drug effects,  metabolism
Forskolin / pharmacology
Gene Knockdown Techniques
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
RNA, Small Interfering / genetics
Signal Transduction
Grant Support
ID/Acronym/Agency:
DK38452/DK/NIDDK NIH HHS; DK43341/DK/NIDDK NIH HHS; DK57521/DK/NIDDK NIH HHS; HD40793/HD/NICHD NIH HHS; HD45821/HD/NICHD NIH HHS; R01 DK097124/DK/NIDDK NIH HHS; R01 HD040793/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 56-65-5/Adenosine Triphosphate; 66428-89-5/Forskolin
Comments/Corrections
Comment In:
J Urol. 2013 Feb;189(2):657   [PMID:  23312197 ]

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


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