| cGMP decreases surface NKCC2 levels in the thick ascending limb: role of phosphodiesterase 2 (PDE2). | |
| | |
MedLine Citation:
|
PMID: 18684888 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
NaCl absorption in the medullary thick ascending limb of the loop of Henle (THAL) is mediated by the apical Na/K/2Cl cotransporter (NKCC2). Hormones that increase cGMP, such as nitric oxide (NO) and natriuretic peptides, decrease NaCl absorption by the THAL. However, the mechanism by which cGMP decreases NaCl absorption in THALs is not known. We hypothesized that cGMP decreases surface NKCC2 levels in the THAL. We used surface biotinylation to measure surface NKCC2 levels in rat THAL suspensions. We tested the effect of the membrane-permeant cGMP analog dibutyryl-cGMP (db-cGMP) on surface NKCC2 levels. Incubating THALs with db-cGMP for 20 min decreased surface NKCC2 levels in a concentration-dependent manner (basal=100%; db-cGMP 100 microM=77+/-7%; 500 microM=54+/-10% and 1,000 microM=61+/-8%). A different cGMP analog 8-bromo-cGMP (8-Br-cGMP) also decreased surface NKCC2 levels by 25%, (basal=100%; 8-Br-cGMP=75+/-5%). Incubation of isolated, perfused THALs with db-cGMP decreased apical surface NKCC2 labeling levels as measured by immunofluorescence and confocal microscopy. cGMP-stimulated phosphodiesterase 2 (PDE2) mediates the inhibitory effect of NO on NaCl absorption by THALs. Thus we examined the role of PDE2 and found that PDE2 inhibitors blocked the effect of db-cGMP on surface NKCC2. Also, a nonstimulatory concentration of db-cAMP blocked the cGMP-induced decrease in surface NKCC2. Finally, db-cGMP inhibited THAL net Cl absorption by 48+/-4%, and this effect was completely blocked by PDE2 inhibition. We conclude that cGMP decreases NKCC2 levels in the apical membrane of THALs and that this effect is mediated by PDE2. This is an important mechanism by which cGMP inhibits NaCl absorption by the THAL. |
| | |
Authors:
|
Gustavo R Ares; Paulo Caceres; Francisco J Alvarez-Leefmans; Pablo A Ortiz |
Related Documents
:
|
10213428 - Hyperkalaemic periodic paralysis in homozygous and heterozygous horses: a co-dominant g... 2071478 - Abortion of a mummified fetus associated with short uterine body in a mare. 22220298 - Clinical inquiry: does cervical membrane stripping in women with group b streptococcus ... 1060838 - Observations on reproductive performance in the yearling mare. 8695628 - Craniofacial morphology in twins with cleft lip and palate. 3127368 - Bovine brucellosis: an investigation of latency in progeny of culture-positive cows. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-08-06 |
Journal Detail:
|
Title: American journal of physiology. Renal physiology Volume: 295 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2008 Oct |
Date Detail:
|
Created Date: 2008-10-10 Completed Date: 2008-12-03 Revised Date: 2011-04-28 |
Medline Journal Info:
|
Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: F877-87 Citation Subset: IM |
Affiliation:
|
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, and Department of Physiology, Wayne State University, 2799 West Grand Blvd., Detroit, MI 48202, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Chlorides / metabolism Cyclic AMP / metabolism Cyclic GMP / analogs & derivatives, metabolism*, pharmacology Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism* Dibutyryl Cyclic GMP / pharmacology Epithelial Cells / enzymology* Loop of Henle / cytology, metabolism* Male Membrane Proteins / metabolism Protein Transport / drug effects, physiology Rats Rats, Sprague-Dawley Signal Transduction / drug effects, physiology Sodium Chloride / metabolism Sodium-Potassium-Chloride Symporters / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
NS29227/NS/NINDS NIH HHS; R0-1 HL-080409/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Chlorides; 0/Membrane Proteins; 0/Sodium-Potassium-Chloride Symporters; 0/sodium-potassium chloride cotransporter 2 protein; 31356-94-2/8-bromocyclic GMP; 32266-35-6/Dibutyryl Cyclic GMP; 60-92-4/Cyclic AMP; 7647-14-5/Sodium Chloride; 7665-99-8/Cyclic GMP; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 2; EC 3.1.4.17/Pde2a protein, rat |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The molecular and functional phenotype of glomerular podocytes reveals key features of contractile s...
Next Document: Increased mast cell number in human hypertensive nephropathy.