Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mammals, the Na+/H+ exchanger 3 (NHE3) is expressed with Na+/K+-ATPase in renal proximal tubules, where it secretes H+ and absorbs Na+ to maintain blood pH and volume. In elasmobranchs (sharks, skates, and stingrays), the gills are the dominant site of pH and osmoregulation. This study was conducted to determine whether epithelial NHE homologs exist in elasmobranchs and, if so, to localize their expression in gills and determine whether their expression is altered by environmental salinity or hypercapnia. Degenerate primers and RT-PCR were used to deduce partial sequences of mammalian NHE2 and NHE3 homologs from the gills of the euryhaline Atlantic stingray (Dasyatis sabina). Real-time PCR was then used to demonstrate that mRNA expression of the NHE3 homolog increased when stingrays were transferred to low salinities but not during hypercapnia. Expression of the NHE2 homolog did not change with either treatment. Rapid amplification of cDNA was then used to deduce the complete sequence of a putative NHE3. The 2,744-base pair cDNA includes a coding region for a 2,511-amino acid protein that is 70% identical to human NHE3 (SLC9A3). Antisera generated against the carboxyl tail of the putative stingray NHE3 labeled the apical membranes of Na+/K+-ATPase-rich epithelial cells, and acclimation to freshwater caused a redistribution of labeling in the gills. This study provides the first NHE3 cloned from an elasmobranch and is the first to demonstrate an increase in gill NHE3 expression during acclimation to low salinities, suggesting that NHE3 can absorb Na+ from ion-poor environments.
 ...
PMID:NHE3 in an ancestral vertebrate: primary sequence, distribution, localization, and function in gills. 1599 75

Experiments were conducted on adult rainbow trout (Oncorhynchus mykiss) to test the hypothesis that SLC9 Na+/H+ exchangers (SLC9A2, NHE2; and SLC9A3, NHE3) on the gill epithelium are localized specifically to a subset of mitochondria-rich cells (MRCs) that are unable to bind peanut lectin agglutinin (PNA). This cell type, termed the PNA- MRC, is a sub-type of MRC believed to function in Na+ uptake and acid excretion. A technique using biotinylated PNA was used to distinguish between the PNA- and PNA+ MRCs on fixed gill sections. In contrast to expectations, both NHE2 (mRNA) and NHE3 (protein) were confined to cells enriched with Na+/K+-ATPase and capable of binding PNA. Thus, in trout, NHE2 and NHE3 are localized to PNA+ MRCs, the cells previously believed to be responsible for Cl- uptake and base excretion. Levels of mRNA for NHE2, the predominant isoform in the gill, were increased during 72 h of hypercapnic acidosis; NHE3 mRNA and protein levels were unaffected. Because plasma cortisol levels were increased during hypercapnia (from 35.3+/-9.4 to 100.1+/-30.9 ng ml(-1)), the effects of experimentally elevated cortisol levels on NHE expression were investigated. The elevation of plasma cortisol using intraperitoneal implants caused a significant increase in NHE2 mRNA expression without affecting NHE3 mRNA or protein abundance. Thus, we suggest that NHE2 contributes to acid-base regulation during hypercapnia owing to its transcriptional regulation by cortisol. The finding of NHE expression in PNA+ MRCs is discussed with reference to current models of ionic and acid-base regulation in teleost fish.
 ...
PMID:Branchial expression and localization of SLC9A2 and SLC9A3 sodium/hydrogen exchangers and their possible role in acid-base regulation in freshwater rainbow trout (Oncorhynchus mykiss). 1862 81

Experiments were performed to assess the possible involvement of the Na(+)/H(+) exchanger isoform 3 (NHE3; SLC9A3) in renal acid-base regulation in adult rainbow trout (Oncorhynchus mykiss). NHE3 mRNA was expressed at high levels in the kidney relative to its paralog, NHE2. The results of in situ hybridization demonstrated an abundance of NHE3 mRNA in renal tubules. The combination of immunocytochemistry and histological staining revealed that NHE3 was confined to the apical membrane of proximal tubules, where it was colocalized with the vacuolar-type H(+)-ATPase. Levels of NHE3 protein (assessed by Western blotting) were increased during hypercapnia, likely as a result of increased transcription, as indicated by increasing levels of NHE3 mRNA (as determined by real-time PCR). Plasma cortisol concentration was increased during hypercapnia, and administration of exogenous cortisol caused a marked increase in NHE3 mRNA and protein. Thus we speculate that the elevation of plasma cortisol during hypercapnia contributes to transcriptional activation of NHE3 that ultimately promotes acid-base regulation by stimulating H(+) secretion and HCO(3)(-) reabsorption.
 ...
PMID:Renal expression and localization of SLC9A3 sodium/hydrogen exchanger and its possible role in acid-base regulation in freshwater rainbow trout (Oncorhynchus mykiss). 1866 17