Document Detail

Activity and regulation of Na+-HCO3- cotransporter in immortalized spontaneously hypertensive rat and Wistar-Kyoto rat proximal tubular epithelial cells.
MedLine Citation:
PMID:  17325238     Owner:  NLM     Status:  MEDLINE    
The present study evaluates the presence and functional proprieties of the Na(+)-HCO(3)(-) cotransporter (NBC) in immortalized renal proximal tubular epithelial cells from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The expected size and nucleotide sequence of a 1031-bp fragment corresponding to type 1 NBC (NBC1) was identified in both cell lines. The expression of the NBC1 transcript was lower (P<0.05) in SHR than in WKY cells. After intracellular acidification and in the presence of amiloride (1 mmol/L), the addition of sodium (115 mmol/L) in the absence of chloride resulted in rapid intracellular pH recovery that was higher in WKY than in SHR cells. This was an Na(+)- and HCO(3)(-)-dependent process in both cell lines. 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulphonic acid inhibited NBC activity in both WKY and SHR cells; the inhibitory effect was, however, more pronounced in WKY than in SHR cells. Forskolin (10 micromol/L) and dibutyryl cAMP (0.5 mmol/L) did not alter NBC activity. Acidosis induced by a 24-hour treatment with NH4(+) (20 mmol/L) increased NBC activity to a greater extent in SHR than in WKY cells, without changes in intracellular pH and cell viability. Treatment with acetazolamide (300 micromol/L) for 24 hours did not change NBC activity in both cell lines. In contrast to NBC, Na(+)-K(+) ATPase activity and expression were higher in SHR than in WKY cells. It is concluded that SHR cells are endowed with lower NBC activity than WKY cells, but the former is more resistant to 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid and responds better to acidosis.
Rui Pedrosa; Nuno Gonçalves; Ulrich Hopfer; Pedro A Jose; Patrício Soares-da-Silva
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-26
Journal Detail:
Title:  Hypertension     Volume:  49     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-19     Completed Date:  2007-05-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1186-93     Citation Subset:  IM    
Institute of Pharmacology and Therapeutics Faculty of Medicine, Porto, Portugal.
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MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
Acidosis / metabolism
Cell Line, Transformed
Epithelial Cells / metabolism
Hypertension / metabolism*,  pathology
Kidney Tubules, Proximal / metabolism*,  pathology
RNA, Messenger / metabolism
Rats, Inbred SHR / metabolism*
Rats, Inbred WKY
Sodium-Bicarbonate Symporters / antagonists & inhibitors,  genetics,  metabolism*
Sodium-Potassium-Exchanging ATPase / metabolism
Reg. No./Substance:
0/RNA, Messenger; 0/Slc4a4 protein, rat; 0/Sodium-Bicarbonate Symporters; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; EC ATPase

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