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PubMed1985

Effect of acute hypercapnia on renal bicarbonate reabsorption in the dog.

The increased plasma bicarbonate concentration seen in hypercapnia implies that tubular bicarbonate reabsorption must be increased in the presence of an elevated Paco2. In contrast to early reports, more recent experimental data in acute hypercapnia have been interpreted to show that the observed increment in tubular reabsorption of bicarbonate factored for glomerular filtration rate (THCO3/GFR) is largely related to the concurrent changes in renal sodium reabsorption and to the increment in the filtered load of bicarbonate, and that acute hypercapnia per se causes little or no change in the tubular handling of bicarbonate. We reexamined this question by observing the changes in renal function occurring in the presence of a moderate elevation of plasma bicarbonate concentration in two groups of dogs. In group I, the elevation occurred as a result of acute hypercapnia during the administration of an "isometric" solution; in group II, it was caused by the infusion of identical amounts of an isotonic solution with the same concentration of sodium as in group I, but a higher bicarbonate concentration, in the presence of eucapnia. A subset of group II provided controls for the decrease in renal perfusion pressure that occurred spontaneously in group I. With increasing filtered loads of bicarbonate, fractional excretion (FE) of HCO3 increased in group II, whereas it dropped markedly in group I. Furthermore, the relative reabsorption rate of HCO3 compared with that of Cl (assessed by changes in fractional reabsorption (FR) of HCO3/Cl) decreased in group II, whereas it increased in group I. Although FENa also decreased in group II, the opposite changes in FR(HCO3/Cl) could not be attributed solely to concurrent changes in sodium handling, indicating that in the presence of acute hypercapnia there is a preferential reabsorption of bicarbonate that tends to perpetuate the increase in plasma bicarbonate concentration. By contrast, THCO3/GFR rose in both groups. The data are interpreted to reveal that acute hypercapnia, although causing a drop in renal perfusion pressure and in natriuresis, also has an additional specific effect on raising preferential bicarbonate reabsorption. This effect can be detected best by monitoring changes in the anionic composition of tubular reabsorbate, whereas it may not be unveiled by following changes in THCO3/GFR. Changes in THCO3/GFR may not yield useful information regarding the integrated response of the kidney to acid-base perturbations, and the conclusions of previous studies based on changes in this parameter must be carefully reexamined.

Absorption↗

PubMed1994

Safety and efficacy of intravenous Carbicarb in patients undergoing surgery: comparison with sodium bicarbonate in the treatment of mild metabolic acidosis. SPI Research Group. Study of Perioperative Ischemia.

OBJECTIVES: To compare the safety and efficacy of intravenous Carbicarb with intravenous sodium bicarbonate in well-oxygenated patients who developed metabolic acidosis while undergoing major surgery. Carbicarb is an equimolar solution of sodium bicarbonate and sodium carbonate (Na2CO3). It does not undergo significant breakdown to CO2 and H2O, nor does it increase CO2 concentrations to the same extent as does pure sodium bicarbonate. Because of these characteristics, Carbicarb may be a more suitable agent than bicarbonate in the treatment of metabolic acidosis. DESIGN: Prospective, double-blind, randomized, multicenter trial. SETTING: Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco), and the University of Massachusetts Medical Center, Worcester, MA. PATIENTS: We prospectively studied 36 patients who underwent either cardiac surgery or major noncardiac surgery and developed intraoperative metabolic acidosis (pH < 7.35 and whose serum bicarbonate concentration decreased by > 3 mmol). INTERVENTIONS: Patients were randomly assigned to receive either sodium bicarbonate (1 mEq sodium/mL, n = 18) or 1 mol Carbicarb (1 mEq sodium/mL, n = 18) administered by intravenous bolus over a 30-sec period. MEASUREMENTS AND MAIN RESULTS: For Carbicarb-treated patients, the mean arterial pH increased from 7.31 +/- 0.008 (baseline) to 7.36 +/- 0.009 10 mins after treatment; for the sodium bicarbonate-treated patients, the mean pH increased from 7.31 +/- 0.006 to 7.37 +/- 0.01. The increases in pH were statistically significant for both groups (p = .0001). There was no statistically significant difference between treatment groups in the number of repetitions of initial dose that was required to correct acidosis. Hemodynamic variables remained unchanged in both treatment groups during the study period, with the exception of the mean cardiac output which increased from 6.1 +/- 0.4 (baseline) to 6.9 +/- 1.4 L/min (60 mins after treatment) in a subset of Carbicarb-treated patients and decreased from 6.7 +/- 1.3 to 6.0 +/- 1.2 L/min in a subset of sodium bicarbonate-treated patients, p = .048 (between groups); and the mean pulmonary artery occlusion pressure decreased from 19 +/- 2 mm Hg (baseline) to 8 +/- 3 mm Hg (45 mins after treatment) in the Carbicarb-treated patients, and decreased from 18 +/- 2 to 13 +/- 4 mm Hg in the sodium bicarbonate-treated patients, p = .012 (between groups). Systemic utilization of lactate increased from 0.3 +/- 1.0 mmol/min (baseline) to 5.6 +/- 4.3 mmol/min (45 mins after treatment) in Carbicarb-treated patients, and increased from 1.0 +/- 0.6 mmol/min (baseline) to 1.5 +/- 1.3 mmol/min in the sodium bicarbonate-treated patients, p = .033 (between groups). The administration of Carbicarb was safe. No patients were discontinued from the study because of adverse events. CONCLUSIONS: Carbicarb corrects metabolic acidosis as well as sodium bicarbonate. However, the potential therapeutic advantage of Carbicarb remains to be determined, especially in patients with more severe metabolic acidosis.

Acidosis↗

PubMed2002

Bicarbonate transport proteins.

Bicarbonate is not freely permeable to membranes. Yet, bicarbonate must be moved across membranes, as part of CO2 metabolism and to regulate cell pH. Mammalian cells ubiquitously express bicarbonate transport proteins to facilitate the transmembrane bicarbonate flux. These bicarbonate transporters, which function by different transport mechanisms, together catalyse transmembrane bicarbonate movement. Recent advances have allowed the identification of several new bicarbonate transporter genes. Bicarbonate transporters cluster into two separate families: (i) the anion exachanger (AE) family of Cl-/HCO3- exchangers is related in sequence to the NBC family of Na+/HCO3- cotransporters and the Na(+)-dependent Cl/HCO3- exchangers and (ii) some members of the SLC26a family of sulfate transporters will also transport bicarbonate but are not related in sequence to the AE/NBC family of transporters. This review summarizes our understanding of the mammalian bicarbonate transporter superfamily.

Amino Acid Sequence↗

PubMed2004

A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice.

OBJECTIVE: To develop a simple, physiologically based mathematical model of pancreatic duct cell secretion using experimentally derived parameters that generates pancreatic fluid bicarbonate concentrations of >140 mM after CFTR activation. METHODS: A new mathematical model was developed simulating a duct cell within a proximal pancreatic duct and included a sodium-2-bicarbonate cotransporter (NBC) and sodium-potassium pump (NaK pump) on a chloride-impermeable basolateral membrane, CFTR on the luminal membrane with 0.2 to 1 bicarbonate to chloride permeability ratio. Chloride-bicarbonate antiporters (Cl/HCO3 AP) were added or subtracted from the basolateral (APb) and luminal (APl) membranes. The model was integrated over time using XPPAUT. RESULTS: This model predicts robust, NaK pump-dependent bicarbonate secretion with opening of the CFTR, generates and maintains pancreatic fluid secretion with bicarbonate concentrations >140 mM, and returns to basal levels with CFTR closure. Limiting CFTR permeability to bicarbonate, as seen in some CFTR mutations, markedly inhibited pancreatic bicarbonate and fluid secretion. CONCLUSIONS: A simple CFTR-dependent duct cell model can explain active, high-volume, high-concentration bicarbonate secretion in pancreatic juice that reproduces the experimental findings. This model may also provide insight into why CFTR mutations that predominantly affect bicarbonate permeability predispose to pancreatic dysfunction in humans.

Animals↗

PubMed1990

Developmental changes in rabbit juxtamedullary proximal convoluted tubule bicarbonate permeability.

The bicarbonate transport rate in neonatal rabbit juxtamedullary proximal convoluted tubules (JMPCT) is lower than that in adults. The reduced rate of transport could be due to a decrease in active bicarbonate transport or an increase in the passive permeability of the tubule to bicarbonate. The present in vitro microperfusion study directly measured the bicarbonate permeability of neonatal and adult JMPCT. Bicarbonate permeability was measured at both slow and fast perfusion rates to simulate the neonatal and adult proximal tubule flow rates, respectively. At 38 degrees C in tubules perfused at 3 nL/min, bicarbonate permeability was 0.29 +/- 0.11 x 10(-5) cm/s in neonates and 1.70 +/- 0.49 x 10(-5) cm/s in adult PCT (p less than 0.05). At a perfusion rate of 10 nL/min, bicarbonate permeability was 0.11 +/- 0.27 x 10(-5) cm/s in neonatal PCT and 2.31 +/- 0.15 x 10(-5) cm/s in adult PCT (p less than 0.05). These results demonstrate that bicarbonate permeability in neonatal JMPCT is significantly lower than that in adult JMPCT. Thus, the lower rate of bicarbonate transport in neonatal PCT is entirely due to a lower rate of active bicarbonate transport.

Animals↗

PubMed1983

Addition of sodium bicarbonate to calf starter rations varying in protein percent.

The influence of added sodium bicarbonate on calf performance and on a possible sparing effect on dietary protein was studied with 48 Holstein calves. Calves were assigned randomly to one of four starter diets containing 10% chopped hay in a 2 X 2 factorial designed experiment: 1) 12% crude protein, 0% sodium bicarbonate; 2) 12% crude protein, 3% sodium bicarbonate; 3) 17% crude protein, 0% sodium bicarbonate; and 4) 17% crude protein, 3% sodium bicarbonate. All calves were fed fermented colostrum for 5 wk and offered their respective starter diets from birth until 10 wk of age. Average daily gains and daily dry matter intakes for wk 0 to 5 were .24, .25; .28, .24; .26, .19; and .27, .24 kg for diets 1 to 4 and for wk 6 to 10 were .52, 1.64; .50, 1.73; .67, 1.78; and .63, 1.87 kg. Addition of sodium bicarbonate (diets 2 and 4) stimulated greater growth (0 to 5 wk) and higher feed intake for the 10-wk trial. Digestibilities of all nutrient measures at wk 9 were lower with added sodium bicarbonate and may be related to higher feed intake. Added sodium bicarbonate did not influence nitrogen digestibility. However, the higher protein diet with sodium bicarbonate improved nitrogen utilization. Rumen samples collected at 9 wk tended to have a higher pH and ratio of acetate: propionate with added sodium bicarbonate. Calves fed the high protein diets gained more weight and consumed more feed than calves fed the low protein diets.

Animals↗

PubMed1990

Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study.

STUDY OBJECTIVE: To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. DESIGN: Prospective, randomized, blinded, crossover study. Each patient sequentially received sodium bicarbonate and equimolar sodium chloride. The order of the infusions was randomized. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Fourteen patients who had metabolic acidosis (bicarbonate less than 17 mmol/L and base excess less than -10) and increased arterial lactate (mean, 7.8 mmol/L). All had pulmonary artery catheters and 13 were receiving catecholamines. MEASUREMENTS AND MAIN RESULTS: Sodium bicarbonate (2 mmol/kg body weight over 15 minutes) increased arterial pH (7.22 to 7.36, P less than 0.001), serum bicarbonate (12 to 18 mmol/L, P less than 0.001), and partial pressure of CO2 in arterial blood (PaCO2) (35 to 40 mm Hg, P less than 0.001) and decreased plasma ionized calcium (0.95 to 0.87 mmol/L, P less than 0.001). Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure (15 to 17 mm Hg, and 14 to 17 mm Hg, P less than 0.001) and cardiac output (18% and 16%, P less than 0.01). The mean arterial pressure was unchanged. Hemodynamic responses to sodium bicarbonate and sodium chloride were the same. These data have more than 90% power of detecting a 0.5 L/min (7%) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride. Even the 7 most acidemic patients (mean pH, 7.13; range, 6.90 to 7.20) had no significant hemodynamic changes after either infusion. CONCLUSIONS: Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients. Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2.

Acidosis, Lactic↗

PubMed2004

Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.

CONTEXT: Contrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy. OBJECTIVE: To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast. DESIGN, SETTING, AND PATIENTS: A prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (> or =97.2 micromol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast. INTERVENTIONS: Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure. MAIN OUTCOME MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast. RESULTS: There were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 [37.1] micromol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 [61.0] micromol/L] for sodium bicarbonate; P =.09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate (mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P =.02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%). CONCLUSION: Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.

Adult↗

PubMed2006

Use of sodium concentration and anion gap to improve correlation between serum chloride and bicarbonate concentrations.

Although most acid-base disorders cause opposite and equal changes in serum chloride and bicarbonate concentrations, this inverse relationship can be distorted by changes in the anion gap and/or water balance. Therefore, we examined the relationship between chloride and bicarbonate before and after adjusting for anion gap and serum sodium concentration. Patients with abnormal electrolytes were grouped by chloride and bicarbonate concentrations (low, normal, and high). Then, chloride and anion gap-adjusted bicarbonate were adjusted for water excess (or deficit), manifesting as hyponatremia (or hypernatremia), after which patients were reclassified. Classification by chloride and bicarbonate changed in 82% of the 135 patients after adjustment for anion gap and sodium. Serum chloride and bicarbonate were each low (concordant) in 23 patients, while 18 had discordant chlorides and bicarbonates (9 low/high, 9 high/low). After adjustments, chloride and bicarbonate were discordant in 40 patients (31 low/high, 9 high/low) and concordant in none. The correlation between serum chloride and bicarbonate improved from -0.459 to -0.998 after adjustments for sodium and anion gap. A very close inverse relationship between serum chloride and bicarbonate concentrations is commonly distorted by concomitant water disturbances and anion gap acidoses in internal medicine patients admitted with electrolyte disorders.

Acid-Base Equilibrium↗

PubMed1989

Influence of bicarbonate on the sensitivity of renin release to sodium chloride.

Juxtaglomerular cells in vitro are sensitive to changes in osmolality, but it is unknown whether volume-regulatory changes in cellular ion fluxes are important for the renin secretory process. The sensitivity of renin release to increases in osmolality by NaCl was therefore tested on superfused rat glomeruli treated with bicarbonate/chloride exchange inhibitor (DNDS), NaCl/KCl cotransport inhibitor (bumetanide), or Na+/H+ antiport inhibitor (amiloride) in the presence or absence of bicarbonate. In addition, the sensitivity to increases in osmolality by addition of sucrose was tested in the presence or absence of bicarbonate. Renin release from time controls superfused with a bicarbonate-free Ringer was identical to release from glomeruli superfused with a bicarbonate Ringer. DNDS (0.11 or 1.1 mM) had no effect on renin release in a bicarbonate Ringer. 30 mM sucrose inhibited renin release independently of bicarbonate. 15 mM NaCl stimulated renin release when bicarbonate was absent, while it caused an inhibition in the presence of bicarbonate. When bicarbonate/chloride exchange was inhibited, addition of NaCl stimulated renin release even when bicarbonate was present. The effect of NaCl on renin release was not affected by amiloride (1 mM) or bumetanide (10 microM). Thus, volume regulatory mechanisms as known from other cells are not involved in the renin secretory response to small increases in NaCl concentration. Furthermore, the sensitivity of renin release to changes in NaCl concentrations is modulated by bicarbonate in a way that depends on a functioning anion-exchange mechanism. The results are compatible with the existence in the membrane of the secretory granule of a Cl-/HCO3- exchange mechanism which mediates exit of Cl-, and thereby attenuates granular swelling and exocytotic release.

Animals↗

PubMed1987

Contraluminal bicarbonate transport in the proximal tubule of the rat kidney.

In order to measure the contraluminal bicarbonate flux in situ we applied the stopped flow capillary microperfusion technique and measured the influx of 14C-bicarbonate buffer into cortical tubular cells at pH 8. It was found that the influx in percent of the starting concentration is larger at 20 mmol/l bicarbonate than at 1 mmol/l, indicating a sigmoidal type influx curve. At 20 mmol/l bicarbonate the influx was inhibited by 44%, when Na+ was replaced by choline. Replacement of gluconate by chloride or sulfate did not change H14CO3- influx. At this bicarbonate concentration, influx is inhibited by 10 mmol/l 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate (DIDS) (22%), 5 mmol/l of the carbonic anhydrase blocker ethoxyzolamide (40%) as well as by 5 mmol/l of the arginine reagent 4-nitrophenylglyoxal (31%). At 1 mmol/l bicarbonate starting concentration, bicarbonate influx was inhibited when chloride in the perfusate was present or when sulphate was added. Replacement of sodium by choline did not change bicarbonate influx. Addition of DIDS and 8-anilino-naphthalene-1-sulfonate (5 mmol/l each) inhibited 1 mmol/l bicarbonate influx 39 and 49%, respectively. The para-amino-hippurate transport blocker dipropylsulfamoyl-benzoate (probenecid), the chloride channel blocker 5-nitro-2'-(3-phenylpropylamino)-benzoate (NPPB), the SH group blocker 2-(3-hydroxymercuri-2-methoxypropyl)-carbamoyl-phenoxyacetate++ + (mersalyl), and formate did not inhibit bicarbonate influx, at 20 and at 1 mmol/l H14CO3- starting concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1980

Evidence for a bicarbonate leak in the proximal tubule of the rat kidney.

To elucidate the mechanism responsible for the establishment of steady state pH at zero net flux (pH infinity) in proximal convoluted tubules, luminal pH was recorded continuously with antimony microelectrodes under three experimental conditions. First: luminal pH in stationary droplets was allowed to reach pH infinity (6.76 +/- 0.07) and then carbonic anhydrase inhibitor benzolamide (3 x 10(-3) mol/l) was superfused on the kidney surface. Following application of benzolamide, luminal pH decreased within seconds (delta pH = -0.27 +/- 0.03 SEM). Second: tubule segments were perfused continuously with MES-buffer containing solution set to a pH of 6.1. Some 1--2 mm distal to the perfusion pipette luminal pH was recorded and was 6.5 +/- 0.04. After superfusion of benzolamide (3 x 10(-3) mol/l) pH decreased (delta pH = -0.15 +/- 0.03). Third: pH in stationary droplets was again allowed to reach PH infinity (6.69 +/- 0.01) and bicarbonate and CO2- free solution (5 mmol/l phosphate set to a pH of 7.4) was microinfused into the adjacent peritubular capillary. Luminal pH again decreased almost immediately (delta pH = -0.23 +/- 0.02). The data are interpreted as evidence for a bicarbonate leak. In a fourth series of experiments, segments of proximal tubules were perfused under benzolamide (0.4 x 10(-6) mol/min) with solutions initially free of bicarbonate or other buffers. In the collected fluid, bicarbonate was determined by a micro-Astrup method. A significant increase of luminal bicarbonate concentration (r = 0.88) indicates a permeability of 0.98 +/- 0.14 x 10(-6) cm2/s of the tubular wall for bicarbonate. Since bicarbonate eventually increases more than 3-fold the equilibrium concentration, collected bicarbonate could not have been formed by H2CO3 or CO2. Bicarbonate enters the luminal fluid and reacts with secreted hydrogen ions to forms carbonic acid. It, therefore, buffers secreted hydrogen ions and increases luminal pH at or below steady state. Inhibition of carbonic anhydrase and lowering of peritubular bicarbonate thus lower pH infinity.

Animals↗

PubMed1985

Vagal stimulation of human gastric bicarbonate secretion.

Gastric bicarbonate secretion in humans was determined in vivo by using a gastric perfusion-aspiration system. A computer calculated the bicarbonate concentration every 30 s throughout the experiment from measurements of the pH and PCO2 in the aspirate. The total bicarbonate concentration was calculated according to the formula of Henderson and Hasselbalch as the sum of free bicarbonate plus the CO2 that was formed during reaction of bicarbonate with hydrogen ions. In 16 subjects basal gastric bicarbonate secretion was 410 +/- 39 mumol/h (mean +/- SEM). After sham feeding using the chew and spit technique to achieve physiologic vagal activation, the gastric bicarbonate secretion rate increased to 692 +/- 67 mumol/h (p less than 0.001). This response of bicarbonate secretion rate to vagal stimulation was independent of the intragastric pH (range 2-7). In 6 subjects the sham-feeding response was almost abolished (88% inhibition) by the anticholinergic drug benzilonium bromide, however, it was unaffected by premedication with indomethacin. The findings demonstrate that the increase in gastric bicarbonate secretion during the cephalic phase of gastric secretion occurs parallel to the increase in acid secretion. It may therefore be regarded as a physiologic response to reinforce the protective mucus-bicarbonate barrier. The response to vagal stimulation seems to be mediated by a muscarinic transmitter and to be independent of intragastric pH and endogenous prostaglandins.

Adult↗

PubMed1993

The enteric nervous system modulates mammalian duodenal mucosal bicarbonate secretion.

BACKGROUND: Interaction of the enteric nerves in regulating mammalian duodenal mucosal bicarbonate secretion is not well understood. The purpose of the present experiments was to evaluate the role of the enteric nervous system on bicarbonate secretion from rabbit duodenal mucosa in vitro. METHODS: Proximal duodenum from male New Zealand White rabbits was stripped of seromuscular layers, mounted in Ussing chambers, and studied under short-circuited conditions. Effects of electrical field stimulation, vasoactive intestinal polypeptide (VIP), carbachol, prostaglandin E2 (PGE2), dibutyryl-cyclic adenosine monophosphate (db-cAMP), and the neurotoxin tetrodotoxin (TTX) and muscarinic blockade by atropine were studied. RESULTS: Electrical field stimulation significantly (P < 0.01) stimulated bicarbonate secretion, short-circuit current (Isc), and electrical potential difference (PD) that was sensitive to both TTX and atropine. VIP-stimulated bicarbonate secretion was significantly inhibited by TTX (-73%), yet Isc and PD remained unchanged. Atropine decreased VIP-induced bicarbonate secretion (-69%) and Isc (-43%). Carbachol-stimulated bicarbonate secretion, Isc, and PD were abolished by atropine, whereas TTX was without affect. Neither TTX nor atropine had a significant effect on PGE2 or db-cAMP-stimulated bicarbonate secretion. CONCLUSIONS: These results suggest that (1) enteric nerve stimulation activates an acetylcholine receptor that in turn stimulates duodenal epithelial bicarbonate secretion; (2) VIP stimulates bicarbonate secretion, in large part, via the enteric nervous system; and (3) PGE2 and cAMP stimulate bicarbonate secretion independent of the enteric nervous system.

Animals↗

PubMed2001

Iron coordination in photosystem II: interaction between bicarbonate and the QB pocket studied by Fourier transform infrared spectroscopy.

The non heme iron environment of photosystem II is studied by light-induced infrared spectroscopy. A conclusion of previous work [Hienerwadel, R., and Berthomieu, C. (1995) Biochemistry 34, 16288-16297] is that bicarbonate is a bidendate ligand of the reduced iron and a monodentate ligand in the Fe(3+) state. In this work, the effects of bicarbonate replacement with lactate, glycolate, and glyoxylate, and of o-phenanthroline binding are investigated to determine the specific interactions of bicarbonate with the protein. Fe(2+)/Fe(3+) FTIR spectra recorded with (12)C- and (13)C(1)-labeled lactate indicate that lactate displaces bicarbonate by direct binding to the iron through one carboxylate oxygen and the hydroxyl group in both the Fe(2+) and Fe(3+) states. This different binding mode with respect to bicarbonate could explain the lower midpoint of the iron couple observed in the presence of this anion [Deligiannakis, Y., Petrouleas, V., and Diner, B. A. (1994) Biochim. Biophys. Acta 1188, 260-270]. In agreement with the -60 mV/pH unit dependence of the iron midpoint potential in the presence of bicarbonate, the proton release upon iron oxidation by photosystem II is directly measured to 0.95 +/- 0.05 by the comparison of infrared signals of phosphate buffer and ferrocyanide modes. This accurate method may be applied to the study of other redox reactions in proteins. The pH dependence of the iron couple is proposed to reflect the deprotonation of D1His215, a putative iron ligand located at the Q(B) pocket, since the signal at 1094 cm(-1) assigned to the nu(C-N) mode of a histidinate ligand in the Fe(3+) state is not observed in the presence of o-phenanthroline. Specific regulation of the pK(a) of D1His215 by bicarbonate is inferred from the absence of the band at 1094 cm(-1) in Fe(2+)/Fe(3+) spectra recorded with glycolate, glyoxylate, or lactate. A broad positive continuum, maximum at approximately 2550 cm(-1), observed in the presence of bicarbonate, but absent with o-phenanthroline or lactate, glycolate, and glyoxylate, indicates a hydrogen bond network from the non heme iron toward the Q(B) pocket involving bicarbonate and His D1-215. Proton release of about 1, measured upon iron oxidation at pH 6 with the latter anions, points to a proton release mechanism different from that involved in the presence of bicarbonate.

Benzoquinones↗

PubMed2005

Escherichia coli cyclopropane fatty acid synthase: is a bound bicarbonate ion the active-site base?

Cyclopropane synthases catalyze the cyclopropanation of unsaturated fatty acid using S-adenosyl-L-methionine as the methylene donor. The crystal structure of three cyclopropane synthases from Mycobacterium tuberculosis showed a bicarbonate ion bound in the active site that was proposed to act as a general base in the reaction mechanism [Huang, C., Smith, V., Glickman, M. S., Jacobs, W. R., and Sacchettini, J. C. (2002) J. Biol. Chem. 277, 11559-11569]. Because the in vitro activity of M. tuberculosis cyclopropane synthases has not yet been reported and because the ligands of the bicarbonate ion are all strictly conserved in cyclopropane synthases, we used the closely related Escherichia coli cyclopropane fatty acid synthase for this study. The putative ligands that share a hydrogen bond with the bicarbonate through their side chains were mutated. H266A, Y317F, E239A, and E239Q mutants were thus constructed and purified, and their catalytic efficiencies were 5.3, 0.7, 0.2, and <0.02%, respectively. C139 that is bound to the bicarbonate by its NH amide had already been mutated to serine in a previous work, and this mutant retains 31% of the activity of the wild-type enzyme. Kinetic analyses and binding studies using spectrofluorimetry showed that these mutations affected the catalytic constant rather than the binding of the substrates. While addition of free bicarbonate had almost no effect on the wild-type enzyme activity, all mutants, with the exception of E239A and E239Q, were rescued by the addition of free bicarbonate. The catalytic efficiencies of the rescued mutants were 85, 16, and 14% for C139S, H266A, and Y317F, respectively. This effect was specific to bicarbonate. The kinetic parameters of the rescued mutants were determined, and it is shown that the rescuing effect is due to an increase in kcat. These data are interpreted by assuming that the E. coli cyclopropane fatty acid synthase specifically binds a bicarbonate ion that is involved in catalysis, as proposed for the M. tuberculosis enzymes, and that mutation of the bicarbonate ligands decreases the affinity for that ion. However, because the E239Q mutation could not be rescued, we propose that E239 forms a catalytic dyad with the bicarbonate to perform the proton abstraction necessary in the chemical pathway to the cyclopropane ring.

Bicarbonates↗

PubMed2000

Bicarbonate accelerates assembly of the inorganic core of the water-oxidizing complex in manganese-depleted photosystem II: a proposed biogeochemical role for atmospheric carbon dioxide in oxygenic photosynthesis.

The proposed role for bicarbonate (HCO(3)(-)) as an intrinsic cofactor within the water-oxidizing complex (WOC) of photosystem II (PSII) [Klimov et al. (1997) Biochemistry 36, 16277-16281] was tested by investigation of its influence on the kinetics and yield of photoactivation, the light-induced assembly of the functional inorganic core (Mn(4)O(y)Ca(1)Cl(x)) starting from the cofactor-depleted apo-WOC-PSII center and free Mn(2+), Ca(2+), and Cl(-). Two binding sites for bicarbonate were found that stimulate photoactivation by accelerating the formation and suppressing the decay, respectively, of the first light-induced assembly intermediate, IM(1) [apo-WOC-Mn(OH)(2)(+)]. A high-affinity bicarbonate site (K(D) </= 10 microM) stimulates both the rate of recovery of O(2) evolving centers and decreases (by a factor of 1.2-3) t(lag), the time for formation of IM(1). This stimulation involves enhanced binding of the initial Mn(2+) and occurs only at concentrations of Mn(2+) at or below the stoichiometric requirements for water oxidation (</=4 Mn/PSII) and disappears above 4 Mn/PSII. The absence of an effect from added bicarbonate on photoactivation kinetics and yield at saturating concentrations of Mn(2+) and Ca(2+) may be due to the availability of atmospheric bicarbonate dissolved in the buffers (approximately 4 microM at pH 6.0) sufficient for photoactivation. The second bicarbonate site also stimulates the rate of formation of IM(1) but has much lower affinity (K(D) approximately millimolar) and becomes observable only at low concentrations of Ca(2+) that are limiting for photoactivation. This stimulation effect appears to occur by complexation of free Ca(2+), thereby reducing its activity in competing with Mn(2+) in the formation of IM(1). Bicarbonate had no effect on the calcium effector site responsible for the rate-limiting dark step of photoactivation (Ca(2+) binding to IM(1)). Four interpretations of the high-affinity bicarbonate effect may be advanced as testable hypotheses: bicarbonate may (1) act as an integral cofactor within the WOC (possible ligand to the first Mn), (2) act as a Bronsted base to accelerate proton release during formation of either the dark precursor [apo-WOC-Mn(OH)(+)] or IM(1) [apo-WOC-Mn(OH)(2)(+)], (3) directly deliver one or more hydroxide ions during formation of the latter two species (with release of CO(2)), or (4) act as a membrane-soluble anion that electrostatically elevates the local concentration of Mn(2+) in PSII. These results support a possible biogeochemical role for bicarbonate in the evolution of the first oxygenic photosynthetic organism. An improvement in the illumination method for photoactivation is presented in which light flashes of increasing duration are used to extend the pre-steady-state lag phase and to suppress photoinhibition, thereby improving the accuracy of t(lag) determination.

Atmosphere↗

PubMed1976

Bicarbonate reabsorption in chronic renal failure.

Bicarbonate reabsorption was studied in dogs before and after induction of renal failure, produced by infarction of one kidney and removal of the contralateral kidney. Glomerular filtration rate and renal plasma flow decreased to 21 and 37% of control values, respectively. Fractional potassium excretion and fractional phosphate excretion increased significantly. Volume expansion resulted in a significant decrease of bicarbonate reabsorption in both control and uremic groups. At comparable levels of fractional chloride excretion, bicarbonate reabsorption was significantly higher in renal failure than in control animals. In the second group of dogs, following induction of renal failure, sodium bicarbonate was given orally in an amount sufficient to neutralize endogenous acid production. Bicarbonate reabsorption was again significantly higher than in control animals. Thyroparathyroidectomy had no effect on bicarbonate reabsorption. Absolute bicarbonate reabsorption and sodium reabsorption were lineraly related in control animals and in those in renal failure; the ratio of absolute bicarbonate reabsorption/abolute sodium reabsorption was significantly higher in renal failure than in control. These data demonstrate that renal failure is associated with enhanced bicarbonate reabsorption which is not related to the state of extracellular volume, the need to increase acid excretion or the concentrations of parathyroid hormone. These findings suggest that there are additional unknown factors controlling bicarbonate reabsorption in renal failure.

Animals↗