HCO3(-) reabsorption in the renal tubules plays a critically important role in maintaining the global acid-base balance. Loss of HCO3(-) causes metabolic acidosis. Proximal renal tubule is the major site for HCO3(-) reabsorption, accounting for more than 80% of total HCO3(-) reabsorption along the nephron. Over the past more than half centuries, tremendous progresses have been made on understanding the molecular mechanisms underlying the HCO3(-) reabsorption in proximal tubules. The transepithelial movement of HCO3(-) involves the coordinated operation of machineries on both the apical and the basolateral membranes of the epithelial cells. On the apical domain, Na(+)-H(+) exchanger NHE3 and the vacuolar H(+)-ATPase are two major pathways mediating the apical uptake of HCO3(-)-related species. Taken together, NHE3 and H(+)-ATPase are responsible for about 80% of HCO3(-) reabsorption in the proximal tubule. The remaining 20% is likely mediated by pathways yet to be characterized. On the basolateral membrane, NBCe1 represents the only major known pathway mediating the extrusion of HCO3(-) coupled with Na(+) into the interstitial space. In the present article, we provide a historical view about the studies on the mechanisms of HCO3(-) reabsorption since 1940s. Moreover, we summarize the latest progresses emerging over the past decade in the physiological as well as pathological roles of acid-base transporters underlying the HCO3(-) reabsorption in proximal tubules.
Acidosis ; physiopathology ; Animals ; Bicarbonates ; metabolism ; Humans ; Kidney Tubules, Proximal ; physiopathology ; Sodium-Hydrogen Exchangers ; physiology ; Vacuolar Proton-Translocating ATPases ; physiology

OBJECTIVETo investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms.

METHODSThe 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence.

RESULTSCompared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01).

CONCLUSIONWLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.

Animals ; Antiporters ; metabolism ; Bicarbonates ; metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gastric Mucosa ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; metabolism

Phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) is an important ubiquitous cytosol enzyme that fixes HCO3 together with phosphoenolpyruvate (PEP) and yields oxaloacetate that can be converted to intermediates of the citric acid cycle. In plant cells, PEPC participates in CO2 assimilation and other important metabolic pathways, and it has broad functions in different plant tissues. PEPC is also involved in the regulation of storage product synthesis and metabolism in seeds, such as affecting the metabolic fluxes from sugars/starch towards the synthesis of fatty acids or amino acids and proteins. In this review, we introduced the progress in classification, structure and regulation of PEPC in plant tissues. We discussed the potential applications of plant PEPCs in genetic engineering. The researches in functions and regulation mechanism of plant PEPCs will provide beneficial approaches to applications of plant PEPCs in high-yield crops breeding, energy crop and microbe genetic engineering.
Bicarbonates ; chemistry ; Genetic Engineering ; Oxaloacetic Acid ; chemistry ; Phosphoenolpyruvate ; chemistry ; Phosphoenolpyruvate Carboxylase ; chemistry ; genetics ; metabolism ; Plants ; enzymology

The short-circuit current (I(SC)) technique was used to examine the effects of cAMP-evoking agents, forskolin/IBMX, and a Chinese medicinal formula, Huoxiang-zhengqi liquid (HZL) on HCO(3)(-) secretion by intact porcine distal airway epithelium. The freshly isolated airway epithelial tissue displayed a transepithelial basal current of (94.9±8.2) μA/cm(2), 16.6% and 62.7% of which was inhibited by amiloride (epithelial Na(+) channel blocker, 100 μmol/L) and NPPB (cystic fibrosis transmembrane conductance regulator Cl(-) channel blocker, 100 μmol/L). Substitution of Cl(-) with impermeable gluconate(-) in the K-H bath solution resulted in a basal current of (54.0±6.7) μA/cm(2), which could be abolished by further removal of HCO(3)(-) in the solution, indicating HCO(3)(-) secretion under unstimulated conditions. Application of forskolin/IBMX (10 μmol/L/100 μmol/L) stimulated an increase of (13.8±1.9) μA/cm(2) in I(SC) which could be blocked by Cl(-) channel inhibitor DPC. With Cl(-) and Cl(-)/HCO(3)(-) substitution, forskolin/IBMX evoked an increase of (7.3±0.5) μA/cm(2) in HCO(3)(-)-dependent, DPC-inhibitable I(SC) (I(HCO(3))). Noticeably, basolateral application of HZL (10 μL/mL) in normal K-H solution evoked an I(SC) of (15.9±2.4) μA/cm(2). The EC(50) of this I(SC) was (6.1±1.4) μL/mL. When substituting Cl(-), HZL stimulated an increase of (7.4±1.9) μA/cm(2) in I(HCO(3)), suggesting HZL-induced HCO(3)(-) secretion. After pretreating the epithelial tissues with forskolin/IBMX in Cl(-)-free K-H solution, HZL induced a further increase of (8.4±0.9) μA/cm(2) in I(HCO(3)), and pretreating tissues with HZL did not significantly affect the subsequent forskolin/IBMX-induced I(HCO(3)) response, indicating that HZL- and forskolin/IBMX-induced I(HCO(3)) responses appeared to be independent and be most likely mediated via different cellular mechanisms. Our results suggest that HCO(3)(-) can be secreted by porcine distal airway epithelium under unstimulated and stimulated conditions, and the stimulatory effect of HZL on HCO(3)(-) secretion in the distal airway epithelium shows HZL to be a hopeful new agonist for distal airway HCO(3)(-) secretion that could be of therapeutic significance.
Amiloride ; pharmacology ; Animals ; Bicarbonates ; metabolism ; Biological Transport ; Colforsin ; pharmacology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Drugs, Chinese Herbal ; pharmacology ; Epithelium ; drug effects ; metabolism ; Respiratory System ; drug effects ; metabolism ; Swine

Pancreatic duct cells secrete HCO3(-) ions into a HCO3(-)-rich luminal fluid (~140 mmol/L in human) against at least a 6-fold concentration gradient. Candidate mechanisms for HCO3(-) transport across the apical membrane include Cl(-)-HCO3(-)exchange by an SLC26 anion transporter and diffusion via the HCO3(-) conductance of cystic fibrosis transmembrane conductance regulator (CFTR). Members of the SLC26 family are known to mediate Cl(-)-HCO3(-) exchange across the apical membrane of other epithelia and both SLC26A6 and SLC26A3 have been detected in pancreatic ducts. Co-expression studies have also revealed that murine slc26a6 and slc26a3 physically interact with CFTR through the STAS domain of slc26 and the R domain of CFTR, resulting in mutually enhanced activity. Other studies have indicated that these exchangers are electrogenic: slc26a6 mediating 1Cl(-)-2HCO3(-) exchange and slc26a3 mediating 2Cl(-)-1HCO3(-) exchange. Recent experiments using isolated pancreatic ducts from slc26a6(-)/(-) mice suggest that slc26a6 mediates most of the Cl(-)-dependent secretion of HCO3(-) across the apical membrane in the mouse and the data are consistent with the reported electrogenicity of slc26a6. However, the role of SLC26A6 in human pancreatic HCO3(-) secretion is less clear because human ducts are capable of secreting much higher concentrations of HCO3(-). The role of SLC26A6 must now be evaluated in a species such as the guinea pig which, like the human, is capable of secreting HCO3(-) at a concentration of ~140 mmol/L. From existing guinea pig data we calculate that a 1Cl(-)-2HCO3(-) exchanger such as slc26a6 would be unable to secrete HCO3(-) against such a steep gradient. On the other hand, the HCO3(-) conductance of CFTR could theoretically support secretion of HCO3(-) to a much higher concentrations. CFTR may therefore play a more important role than SLC26A6 in HCO3(-) secretion by the guinea pig and human pancreas.
Animals ; Bicarbonates ; metabolism ; Chloride-Bicarbonate Antiporters ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; physiology ; Guinea Pigs ; Humans ; Membrane Transport Proteins ; physiology ; Mice ; Pancreatic Ducts ; cytology ; secretion

Cystic fibrosis (CF) of the pancreas is the most widely accepted name of the most common fatal inherited single gene defect disease among Caucasians. Its incidence among other races is thought to be significantly less, but mutations in the gene have been reported in most, if not all, major populations. This review is intended to give general concepts of the molecular as well as physiological basis of the pathology that develops in the disease. First, an overview of the organ pathology and genetics is presented, followed by the molecular structure of the gene product (cystic fibrosis transmembrane conductance regulator, CFTR), its properties, functions, and controls as currently understood. Second, since mutations appear to be expressed primarily as a defect in electrolyte transport, effects and mechanisms of pathology are presented for two characteristically affected organs where the etiology is best described: the sweat gland, which excretes far too much NaCl ("salt") and the pancreas, which excretes far too little HCO3(- )("soda"). Unfortunately, morbidity and mortality in CF develop principally from refractory airway infections, the basis of which remains controversial. Consequently, we conclude by considering possible mechanisms by which defects in anion transport might predispose the CF lung to chronic infections.
Anions ; metabolism ; Bicarbonates ; Cystic Fibrosis ; physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Humans ; Ion Transport ; Pancreas ; physiopathology ; Sodium Chloride ; Sweat Glands ; physiopathology

Luminal acidification in the epididymis is an important process for the regulation of male fertility. Low pH and low bicarbonate concentration are among key factors that keep spermatozoa in a dormant state while they mature and are stored in this organ. Although significant bicarbonate reabsorption is achieved by principal cells in the proximal regions of the epididymis, clear and narrow cells are specialized for net proton secretion. Clear cells express very high levels of the vacuolar proton pumping ATPase (V-ATPase) in their apical membrane and are responsible for the bulk of proton secretion. In the present paper, selected aspects of V-ATPase regulation in clear cells are described and potential pathologies associated with mutations of some of the V-ATPase subunits are discussed.
Adenosine Triphosphatases ; metabolism ; Adenylyl Cyclases ; metabolism ; Animals ; Bicarbonates ; metabolism ; Epididymis ; metabolism ; Humans ; Hydrogen-Ion Concentration ; Male ; Mice ; Proton Pumps ; metabolism ; Vacuoles ; enzymology

The luminal fluid environment of the female reproductive tract is considered critical for the sperm to undergo a series of molecular events leading to the final acquisition of their fertilizing capacity. It has been shown that the fluid in the female reproductive tract contains high content of HCO3- and it plays an important role in sperm functions including sperm motility, capacitation, hyperactivation and acrosome reaction. This review summarizes the effects of HCO3- on sperm functions occurring in the female reproductive tract and discusses the transport mechanisms involved in mediating uterine HCO3- secretion. New evidence is also presented to show possible cause of female infertility due to defective HCO3- transporting mechanism.
Animals ; Bicarbonates ; metabolism ; Female ; Fertilization ; physiology ; Humans ; Male ; Sperm Capacitation ; physiology ; Sperm-Ovum Interactions ; physiology ; Uterus ; metabolism ; secretion

OBJECTIVETo study the difference of plasma actual bicarbonate between the children with growth hormone deficiency (GHD) and idopathatic short stature (ISS) and to value the plasma bicarbonate standard deviation scores (SDS) in diagnosis of GHD.

METHODSForty-seven short stature children were divided into two groups (GHD and ISS) according to the peak GH response to provocative test. Plasma actual bicarbonate concentrations anion gap (AG), base excess and electrolytes were measured in 47 children with short stature before GH provocative tests.

RESULTSThe mean plasma actual bicarbonate concentrations, bicarbonate SDS were (22.60+/-1.29)mmol/L and -0.27+/-0.98 respectively in GHD children, which were significantly lower than those of ISS children (P<0.01), whereas AG was higher than that of ISS children [(11.73+/-4.52 vs 7.87+/-1.70) mmol/L], P<0.01. Seventy-two percent of patients with bicarbonate SDS

CONCLUSIONPlasma actual bicarbonate concentrations and bicarbonate SDS are lower in patients with GHD than those in patients with idopathatic short stature. Evaluation of plasma bicarbonate SDS of short stature children can predict the probability of GHD, especially when bicarbonate SDS is less than 1 s.

Acid-Base Equilibrium ; Adolescent ; Bicarbonates ; blood ; Child ; Child, Preschool ; Female ; Growth Disorders ; metabolism ; Human Growth Hormone ; deficiency ; Humans ; Male

The physiological changes that occur to sperm during the residence in the female tract are collectively referred to as "capacitation". The mechanism of action by which these compounds promote capacitation is poorly understood at the molecular level. However, some molecular events significant to the initiation of capacitation have been identified, such as the correlation of capacitation with cholesterol efflux from the sperm plasma membrane, increased membrane fluidity, modulations in intracellular ion concentrations, hyperpolarization of the sperm plasma membrane and increased protein tyrosine phosphorylation. This review discusses recent progress in elucidation mechanisms which regulate sperm capacitation.
Bicarbonates ; metabolism ; Calcium ; metabolism ; Cholesterol ; metabolism ; Cyclic AMP ; physiology ; Humans ; Ion Transport ; Male ; Membrane Potentials ; Phosphorylation ; Sperm Capacitation