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PubMed1994

Role of dopamine and other stimuli of mucosal bicarbonate secretion in duodenal protection.

Duodenal mucosal secretion of bicarbonate is one main mechanism in the protection of this epithelium against luminal acid. The duodenal secretagogue vasoactive intestinal polypeptide, at doses not affecting mucosal blood flow, protects against acid-induced morphological changes. Some sigma receptor ligands, which increase the duodenal alkaline secretion, prevent duodenal but not gastric mucosal ulceration. Dopamine D-1 receptor agonists and the peripherally acting catechol-O-methyl-transferase (COMT) inhibitor nitecapone stimulate the bicarbonate secretion in the rat and a similar increase in secretion has been observed in human volunteers. COMT inhibitors decrease tissue degradation of catecholamines, including dopamine. The D-2 agonist bromocriptine, in contrast, decreases the secretion. These results, indicating that the bicarbonate secretion is stimulated via peripheral dopamine D-1 receptors, are supported by the finding that dopamine D-1 (but not D-2) agonists increase the production of cyclic AMP in isolated duodenal enterocytes. The increase in mucosal alkaline secretion may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.

Animals↗
PubMed1994

A kinetic model of rat proximal tubule transport--load-dependent bicarbonate reabsorption along the tubule.

A model is presented of solute and water reabsorption along the proximal tubule of the rat kidney based on kinetic descriptions of the main membrane transport systems, in order to assess the extent to which these kinetics suffice to explain certain aspects of the global transport behaviour in this segment, especially with respect to bicarbonate reabsorption. The model includes in the apical membrane, an active proton pump, Na+/H+ antiport, Na-coupled transport of organic solutes, Cl-/formate exchange with formic acid recycling, and membrane conductances to protons and K+. In the baso-lateral membrane, besides the Na+/K+ pump, the model includes Na(+)-3HCO3- and electroneutral K(+)-Cl- cotransporters, and membrane conductances for K+, H+, and, optionally, for Cl-. Appropriate passive diffusional pathways were included in both cell membranes and in the paracellular pathway. Using mass balance and electroneutrality constraints, these transport systems were built into an epithelial model which was then integrated (by finite difference approximation) into a model of a longitudinal tubule. Simulated cellular solute concentrations and luminal concentration profiles were in good agreement with reported experimental observations. We show that, given the reported transport kinetics for the Na+/H+ antiporter, a hitherto unexplained observation concerning load-dependent bicarbonate reabsorption can be shown mainly to result from the nonlinear longitudinal concentration profile for bicarbonate and pH. We also discuss problems of transcellular Cl- transport in the light of recent reports of basolateral Cl- conductance and observations relevant to apical Cl-/formate (or other base) exchange.

Absorption↗
PubMed1999

Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis.

UNLABELLED: In this study the effectiveness of 4.5% human albumin was compared with 4.2% sodium bicarbonate for neonatal metabolic acidosis, using a randomised controlled trial. The change in median pH following bicarbonate was more than twice that in the albumin group. This was statistically significant. CONCLUSION: In normotensive infants, use of bicarbonate to correct metabolic acidosis may be more effective than use of albumin.

Acidosis↗
PubMed1985

Umbilical cord pH, PCO2, and bicarbonate following uncomplicated term vaginal deliveries.

Normal values for umbilical arterial and venous pH, PCO2, PO2, and bicarbonate must be known before these parameters can be used for assistance in clinical decisions. We evaluated the cord blood from 146 infants born after uncomplicated labor and vaginal deliveries at 37 to 42 weeks' gestation. All infants had a normal baseline fetal heart rate and normal beat-to-beat variability for at least 10 minutes preceding expulsion. The cord blood of infants born to women with pregnancy complications such as diabetes mellitus, preeclampsia, twins, meconium-stained amniotic fluid, or fetal growth retardation was not included. Mean umbilical arterial values +/- 1 SD for the parameters studied were: pH, 7.28 +/- 0.05; PCO2, 49.2 +/- 8.4 mm Hg; PO2, 18.0 +/- 6.2 mm Hg; bicarbonate, 22.3 +/- 2.5 mEq/L. Umbilical venous values were: pH, 7.35 +/- 0.05; PCO2, 38.2 +/- 5.6 mm Hg; PO2, 29.2 +/- 5.9 mm Hg; bicarbonate, 20.4 +/- 4.1 mEq/L.

Bicarbonates↗
PubMed1977

Site of bicarbonate effect in Hill reaction. Evidence from the use of artificial electron acceptors and donors.

Using artificial electron donors and acceptors, it is shown here that the major HCO3- effect in the Hill reaction is after the "primary" electron acceptor (Q) of Photosystem II and before the site of action of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (at the plastoquinone pool). Chloroplasts in the presence of both 3-(3',4'-dichlorophenyl)-1,1-dimethylurea, which blocks electron flow from the reduced primary acdeptor Q- to the plastoquinone pool, and silicomolybdate, which accepts electrons from Q-, show no significant bicarbonate stimulation of electron flow. However, a 6-7 fold stimulation is clearly observed when oxidized diaminodurene, as an electron acceptor, and dibromothymoquinone, as an inhibitor of electron flow beyond the plastoquinone pool, are used. In the same chloroplast preparation no measurable effect of bicarbonate is observed in a Photosystem I reaction as monitored by electron flow from reduced diaminodurene to methyl viologen in the presence of 3- (3',4'-dichlorophenyl)-1,1-dimethylurea. The insensitivity of the bicarbonate effect to uncouplers of photophosphorylation and the dependence of this effect on the presence of a weak acid anion and on external pH are also reported.

Bicarbonates↗
PubMed1994

The effect of bicarbonate-free artificial cerebrospinal fluid on spontaneous oscillations of the membrane potential in inferior olivary neurons of the rat.

The membrane potential of mature inferior olivary (IO) neurons oscillates spontaneously at frequencies up to about 10 Hz. This behavior has been attributed to the complement of membrane conductances in these cells and electronic coupling of the neurons via dendro-dendritic gap junctions. In this study intracellular recordings of transmembrane potentials were made in 52 neurons in brainstem slices from rats aged 8-23 days postnatal. During the recordings in 31 neurons the extracellular solution was exchanged from a bicarbonate- to a tris-buffered solution with constant pH. In all cells the spontaneous oscillations of the membrane potential ceased within a few minutes and in 14 of these cells the oscillations resumed with re-exposure to bicarbonate-buffered solution. The spontaneous oscillations in another 6 neurons also ceased when they were exposed to bicarbonate-buffered solution containing 10 mmol NH4Cl. These experimental manipulations produce a rise in intracellular pH despite constant extracellular pH. The low- and high-threshold potentials associated with voltage-sensitive calcium conductances in these neurons and the large hyperpolarization that follows these potentials were unaffected by substitution of the extracellular solution. However, the anomalous rectification of the membrane potential in these neurons (which could be abolished by exposure of the neurons to 2 mM CsCl) was significantly increased by 12.6% in the tris-buffered solution. The data are consistent with the hypothesis that the continuity of oscillations of the membrane potential in IO neurons depends on the transfer of current between the dendro-dendritic junctions and the soma of each neuron. This transfer is reduced when rectifying K+ conductances in the neurons are increased and the ensemble properties of the group of neurons, and the membrane potential oscillations, are lost.

Ammonium Chloride↗
PubMed1992

Stimulation of bicarbonate secretion by atypical beta-receptor agonists in rat cecum in vitro.

This study examined the effects of beta-adrenoceptor agonists on bicarbonate secretion by the rat cecum in vitro. Isoprenaline, the beta 2-selective agonist salbutamol and the 'atypical' beta-agonist SR58611A stimulated bicarbonate secretion in a concentration related manner. Another atypical agonist, BRL 37344, also stimulated. Responses to isoprenaline were antagonised by alprenolol and propranolol (both 20 microM) but not the selective antagonists practolol (10 microM) or ICI 1185511 (1 microM). Responses to SR 58611A were only antagonised by alprenolol. Replacement of Cl- by NO3- on the mucosal surface reduced basal secretion and abolished the response to isoprenaline. Exposure to a single concentration of atypical agonist resulted in desensitisation to a second application and to isoprenaline. There was no evidence of desensitisation with isoprenaline or salbutamol. The results show that beta-adrenoceptor agonists stimulated bicarbonate secretion in contrast to the previously described inhibitory effect of cholinergic drugs in this tissue. Stimulation was mediated by beta-adrenoreceptors, which had properties consistent with the atypical receptors described in gut smooth muscle and in adipose tissue. Both adrenergic and cholinergic drugs may act on the same mechanism of secretion which may involve an exchange of HCO3- for mucosal Cl-.

Adrenergic beta-Agonists↗
PubMed1992

Structure of cobalt carbonic anhydrase complexed with bicarbonate.

The three-dimensional structure of a complex between catalytically active cobalt(II) substituted human carbonic anhydrase II and its substrate bicarbonate was determined by X-ray crystallography (1.9 A). One water molecule and two bicarbonate oxygen atoms are found at distances between 2.3 and 2.5 A from the cobalt ion in addition to the three histidyl ligands contributed by the peptide chain. The tetrahedral geometry around the metal ion in the native enzyme with a single water molecule 2.0 A from the metal is therefore lost. The geometry is difficult to classify but might best be described as distorted octahedral. The structure is suggested to represent a water-bicarbonate exchange state relevant also for native carbonic anhydrase, where the two unprotonized oxygen atoms of the substrate are bound in a carboxylate binding site and the hydroxyl group is free to move closer to the metal thereby replacing the metal-bound water molecule. A reaction mechanism based on crystallographically determined enzyme-ligand complexes is represented.

Bicarbonates↗
PubMed1985

The influence of bicarbonate ions on the GABA-mimetic activity of ethylenediamine.

A study was performed to investigate the GABA-mimetic activity of ethylenediamine (EDA) and piperazine at mammalian gamma-aminobutyric acid (GABA) receptors using radioligand binding assays and in vitro isolated tissues. The potency of ethylenediamine and piperazine as inhibitors of the binding of GABA receptors to synaptic membranes from rat brain was measured in Tris-buffers and Krebs-Henseleit solution (KHS). The potency of ethylenediamine and piperazine at GABAA and ethylenediamine at GABAB receptors was raised if Krebs-Henseleit solution was used for the assay. Piperazine was inactive at GABAB receptors. The potency of the antagonist of GABAA receptors bicuculline methobromide, was also increased in Krebs-Henseleit when compared with Tris-citrate buffer. Of the ions present in Krebs-Henseleit, bicarbonate ions were responsible for the increase in the GABA-mimetic potency of ethylenediamine and piperazine. Addition of either NaHCO3 or KHCO3 (25 mM) to Tris-HCl buffer (for GABAA binding) or Tris-HCl plus 2.5 mM CaCl2 (for GABAB binding) yielded IC50 values similar to those measured in Krebs-Henseleit solution. Bicarbonate ions also enhanced the ability of ethylenediamine to potentiate the binding of [3H]diazepam to membranes from rat brain (raising both the potency of ethylenediamine and its maximum effect) in this system. In the absence of HCO-3 ions, ethylenediamine potentiated the binding of [3H]diazepam by raising the maximum binding capacity (Bmax) without changing the affinity (Kd) of the receptors. Potassium bicarbonate (25 mM) caused ethylenediamine to further potentiate the binding of [3H]diazepam by changing both Bmax and Kd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The use of 36Cl- to measure cell plasma membrane potential in isolated hepatocytes--effects of cyclic AMP and bicarbonate ions.

The plasma membrane potential of hepatocytes was calculated from the distribution of 36Cl-. The potential observed under several conditions was equivalent to that previously measured using microelectrodes in perfused liver. Dibutyryl cAMP increased the membrane potential. Replacement of bicarbonate ions by morpholinosulphonate decreased the potential and reduced the effect of cAMP. The effect of both bicarbonate and cAMP was abolished by ouabain. Both bicarbonate and cAMP stimulated the activity of the (Na+ + K+)-ATPase as measured by ouabain-inhibitable 86Rb+ uptake. It is suggested that the stimulation of alanine transport by these effectors is mediated by an increase in cell membrane potential via stimulation of the (Na+ + K+)-ATPase.

Alanine↗
PubMed1995

A modified Shigella volunteer challenge model in which the inoculum is administered with bicarbonate buffer: clinical experience and implications for Shigella infectivity.

In the absence of a definitive immunologic correlate of protection against shigellosis, promising Shigella vaccine candidates have been selected based on their ability to confer resistance against experimental challenge with wild-type Shigella in healthy adult volunteers. A limitation of this model has been the low and often variable attack rate of illness among controls, necessitating repeated inpatient studies to demonstrate statistically significant results. In this study, the Shigella challenge model was modified by using bicarbonate buffer instead of skimmed milk as the delivery vehicle to enhance survival of the ingested challenge inoculum. To determine the ability of the modified model to detect protective efficacy, 11 veteran volunteers (previously challenged with S. flexneri 2a in bicarbonate buffer) and 12 immunologically naive control subjects were challenged with 1.4 x 10(3) c.f.u. S. flexneri 2a. Shigellosis occurred in 3 veterans and 11 control subjects (27 vs 92%, p = 0.003), yielding a protective efficacy of 70%. Dose response was evaluated in an additional seven naive subjects who were inoculated with a log lower (1.4 x 10(2) c.f.u.) S. flexneri 2a and had a significantly diminished attack rate of shigellosis (317 (43%) vs 11/12 (92%), p = 0.04). These findings indicate that the modified bicarbonate challenge model using an inoculum of 10(3) c.f.u. is a safe, repeatable, and valid method of selecting Shigella vaccines and other immunoprophylactic agents that are likely to confer protection against natural shigellosis.

Adolescent↗
PubMed1995

Bicarbonate dialysate for continuous renal replacement therapy in intensive care unit patients with acute renal failure.

Lactate-buffered peritoneal solution traditionally has been used as dialysate for continuous renal replacement therapy (CRRT) in the United States because no bicarbonate solution is commercially available. Since 1994, the Cleveland Clinic Foundation Dialysis Unit has prepared a bicarbonate solution (sodium 144 +/- 3 mEq/L, HCO3 37 +/- 2 mEq/L, potassium 3 or 4 mEq/L, calcium 3.0 +/- 0.3 mEq/L, and magnesium 1.4 +/- 0.3 mg/dL) replicating the dialysate for chronic intermittent hemodialysis. No solute precipitation, as calcium or magnesium salts, were observed, and several cultures of the solution, performed at various time periods, remained negative. Fifty critically ill acute renal failure patients have been treated with bicarbonate-CRRT. All patients were in multiple organ failure and required mechanical ventilation; 37 were receiving vasopressors. Forty-four continuous venovenous hemodialysis sessions and eight continuous arteriovenous hemodialysis sessions were performed with a mean duration of 7.8 +/- 6.1 days. The mean inflow dialysate rate was 1,249 +/- 225 mL/hr and the mean outflow rate (dialysate plus ultrafiltration) was 1,399 +/- 237 mL/hr; the inflow rate was constantly kept lower or equal to the outflow rate to avoid an enhanced potential for backfiltration. No related fever spikes or sepsis episodes were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Inadequate bicarbonate resuscitation in trauma patients requiring crossclamping of the aorta.

The use of bicarbonate in the management of metabolic acidosis is controversial. We present three patients who required crossclamping of the aorta for control of shock and whose metabolic acidosis was inadequately treated with bicarbonate. Within minutes of aortic declamping, all became hypotensive and two went into refractory ventricular fibrillation and died. Arguments supporting the role of adequate bicarbonate resuscitation in this setting are discussed.

Acidosis↗
PubMed1982

A comparative study of chloride, bicarbonate and water transport by terminal ileum of Canis familiaris, Oryctolagus cuniculus and Capra hircus.

1. The differences in the movement of chloride, bicarbonate and water across the ileal wall has been studied in dog, rabbit and goat both in conscious and anesthetized animals. 2. The rate and direction of chloride transport rely on its intraluminal levels for the three species considered. 3. Chloride absorption by dog ileum is higher than in rabbit and goat. 4. There is a relationship between the net movement of bicarbonate and its luminal concentration for the three species studied. 5. The trend to bicarbonate secretion is lower in dog than in rabbit and goat. 6. Under the same experiment conditions, water is absorbed by the dog ileum while it is secreted by this intestinal portion in rabbit and goat.

Animals↗
PubMed1985

The sodium and bicarbonate dependence of bile secretion in the guinea-pig.

The effects of the total substitution of sodium by lithium, and of bicarbonate by a mixture of chloride and phosphate, on the flow and composition of bile was studied in the isolated perfused guinea-pig liver using a single-pass perfusion system. 60% of secretion was bicarbonate dependent and 80% specifically required the presence of sodium. The secretion of bicarbonate in bile against a concentration gradient was inhibited by the presence of lithium. In contrast to the results of similar studies in the rat, lithium is not an effective substitute for sodium in maintaining bile secretion.

Animals↗
PubMed1990

Sodium- and bicarbonate-independent regulation of intracellular pH in culture mouse astrocytes.

The intracellular pH (pHi) of cultured mouse astrocytes was measured with double-barrelled pH-sensitive microelectrodes. In bicarbonate-buffered saline pHi was 7.05 and in HEPES-buffered saline 6.68. In both solutions H+ was not in electrochemical equilibrium; pHi was 0.7-1 pH unit more alkaline than expected from passive H+ distribution. Cells were acidified by applying NH4+ and the subsequent regulation of pHi was studied in bicarbonate-free saline. The mean rate of pHi recovery was 0.2 pH units min-1 which was not changed by amiloride or by removal of external Na+. Thus, the cells recovered from an acid load independently of Na(+)-H+ exchange, Na(+)-HCO3- cotransport or any other bicarbonate- or Na(+)-dependent mechanism.

Amiloride↗
PubMed1976

Effect of the CO-2-bicarbonate buffer system on the water and ion contents of rat renal cortical slices.

(1) Partial replacement of medium chloride by bicarbonate, with pHmaintained constant by addition of CO2, lead to a greater rate of swelling when rat renal corti cal slices were leached in nitrogenated medium at 0--2 degree C. This greater rate of swelling was still present when 1 mM iodoacetate was added to the leaching media. (2) Rat renal cortical slices incubated in oxygenated bicarbonate medium at 25 degree C maintained a slightly greater tissue water content than did slices incubated in phosphate-buffered media. Inclusion of malate in the incubation medium also led to a greater steady-state water content when slices were incubated at 25 degree C in oxygenated media. These results suggest that that particular cell volume which is maintained by metabolism and the double Donnan system is determined at least in part by the nature of the extracellular anions. (3) The rates of net sodium extrusion and of net potassium uptake were not significantly altered by presence of CI2 and bicarbonate in the incubation medium.

Animals↗
PubMed1980

Gastric bicarbonate secretion: an update.

In vitro and in vivo studies have demonstrated that gastric fundic and antral mucosa secretes a bicarbonate (HCO3-)-rich fluid under a variety of experimental conditions. Bicarbonate secretion appears to be an active, energy requiring process which is thought to occur at the surface epithelial cell. Transmembrane HCO3- transport, isotopic (H14CO3) flux, pH stat titration and pCO2 measurement has been used to indicate HCO3- secretion. Bicarbonate secretion is stimulated by cholinergic agents, dibutyryl-cGMP, calcium, and 16-16-dimethyl prostaglandin E2. Atropine inhibits carbachol-stimulated HCO3- secretion but has no effect on basal HCO3- secretion. Agents which have been shown to inhibit HCO3- secretion are acetazolamide, O2 deprivation, noradrenalin, aspirin and indomethacin. It is plausible to suppose that HCO3- secretion may play a role in protection of the gastric mucosal epithelium. Although for a given area of gastric mucosa, the amount of HCO3- secreted is only about 5 to 10% of the maximal acid output, the neutralizing capability of the HCO3- rich fluid may be significantly greater at the apical cell membrane of the surface epithelial cells.

Animals↗