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Chemical Compound Review

Bicarbonate ion     hydroxymethanoate

Synonyms: bicarbonate, HYDROXYFORMATE, HCO3, Acid carbonate, HCO3-, ...
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Disease relevance of carbonic acid

  • Carbonic anhydrase accelerates the hydration/dehydration reaction between CO(2), HCO(3)(-), and H(+) [1].
  • The loss of this uniquely regulated HCO3- conductance is most probably responsible for the more severe forms of cystic fibrosis pathology [2].
  • Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3- transport, and those associated with pancreatic sufficiency show reduced HCO3- transport [3].
  • Metabolic acidosis causes a reversal of polarity of HCO(3)(-) flux in the cortical collecting duct (CCD) [4].
  • Studies were undertaken in Munich-Wistar rats to determine whether maintenance of chronic metabolic alkalosis (CMA) is associated with an increase in proximal HCO3- reabsorption, or whether a reduction in glomerular filtration rate (GFR) is required to sustain the elevated plasma HCO3- concentration [5].
 

Psychiatry related information on carbonic acid

  • We thus compared the effects of orexin A and some established secretagogues on duodenal HCO3- secretion in fed rats with effects in rats exposed to short (overnight) food deprivation [6].
  • Vagal stimulation (10 Hz for 10 min) increased gastric and duodenal HCO3- secretions, as well as gastric motor activity and H+ secretion [7].
  • Recent reports, including the present one, strongly suggest that Lithium Carbonate may be the treatment of choice for the Kleine-Levin Syndrome [8].
  • Optimum conditions for this new procedure were: hydrogencarbonate-carbonate buffer, pH 10.5, 5-min reaction time at 25 degrees C and an NQS concentration of 7.1x10(-3) mol l(-1) [9].
 

High impact information on carbonic acid

  • This collapse of the surface pH gradients may reflect, at least in part, that such studies have been mostly performed on non-acid-secreting mucosa where the supply of HCO3- to the interstitium from the parietal cells will be reduced [10].
  • Passive diffusion of intestinal HCO3- into the lumen is particularly important when there is superficial damage resulting in increased leakiness of the mucosal epithelium [10].
  • This is amply illustrated within the gastric glands that do not secrete mucus and HCO3- yet are exposed to undiluted pepsin and an isotonic solution of HCl [10].
  • It is expressed on apical membranes of renal proximal tubule and intestinal epithelial cells and is thought to play a major role in NaCl and HCO3- absorption [11].
  • HCO3- and fluid absorption are sharply reduced in proximal convoluted tubules, blood pressure is reduced and there is a severe absorptive defect in the intestine [11].
 

Chemical compound and disease context of carbonic acid

  • This reflects a general sensitivity of this reaction to halides and other anions, up to 87 times greater than the effect on red cell carbonic anhydrase C. The catalytic hydration of CO2 is generally more (up to 24 times) sensitive to inhibition by anions and sulfonamides than the dehydration of HCO3-, probably reflecting different mechanisms [12].
  • These findings, furthermore, offer a possible explanation for the puzzling observation that plasma [HCO3] in patients with the syndrome of inappropriate antidiuretic hormone secretion is maintained at normal levels even in the face of severe hyponatremia [13].
  • DOCA, but not acidosis, increased (approximately 40%) initial pHi response to bath HCO3- or Cl- reduction in Na(+)-free condition [14].
  • These findings indicate that LPS reduces bile acid-independent bile flow primarily by inhibiting biliary excretion of glutathione and to a lesser extent HCO3-, whereas LPS-induced NO does not modulate bile formation in endotoxemia [15].
  • The omission of HCO3- from the extracellular medium or the incubation in acidic conditions also prevented menadione toxicity, without interfering with the loss of mitochondrial membrane potential and with ATP depletion [16].
 

Biological context of carbonic acid

  • It performs two critical biological functions: maintaining ionic homeostasis, by transporting Cl- and HCO3-ions, and providing mechanical stability to the erythroid membrane [17].
  • Cell growth factors. Bicarbonate and pHi response [18].
  • The cell depolarization induced by Cl- channel activation should enhance HCO3- entrance through electrogenic Na+/HCO3- symport, which in turn stimulates the Cl-/HCO3- exchange [19].
  • Apical Na/H antiport activity plays an important role in transcellular bicarbonate (HCO3-) reabsorption, whereas basolateral Na/H antiport activity could be involved in transcellular HCO3- secretion as well as cell volume and pH control [20].
  • MCD HCO3 efflux exhibited saturable kinetics for extracellular Cl, with a Michaelis constant (Km) of 29.9 +/- 7.7 mM [21].
 

Anatomical context of carbonic acid

  • We show that when it is expressed in Xenopus oocytes, this protein is electrogenic, Na+ and HCO3- dependent, and blocked by the anion-transport inhibitor DIDS, and conclude that it is the renal electrogenic sodium bicarbonate cotransporter (NBC) [22].
  • In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts [23].
  • The HCO3- secreting cell in the cortical collecting tubule is found to be an intercalated cell possessing a Cl-/HCO3- exchanger in the apical membrane and proton pumps in endocytic vesicles that fuse with the basolateral membrane; the H+-secreting cell in the medullary collecting tubule has these transport functions on the opposite membranes [24].
  • Primary cultures and plasma membrane vesicles were used to characterize Na+ and HCO3- transport by rat hepatocytes [25].
  • To determine whether cAMP also stimulates HCO3- secretion, we studied cultured canine and human airway epithelial cells bathed in a HCO3-/CO2-buffered, Cl(-)-free solution [26].
 

Associations of carbonic acid with other chemical compounds

  • Here we report phosphorylation- and ATP-independent activation of CFTR by cytoplasmic glutamate that exclusively elicits Cl-, but not HCO3-, conductance in the human sweat duct [2].
  • HCO3 secretion also showed saturation kinetics as a function of mean luminal [Cl] (Km, 4-11 mM) [27].
  • In eight studies of six animals HCO3- concentration fell (from 21.3 to 15.8 meq/liter; P less than 0.001) and lactate concentration rose (from 2.5 to 4.2 meq/liter; P less than 0.05) in the cisternal cerebrospinal fluid during the CO-induced hyperpnea [28].
  • The combined results of the plasma-like and chloride-free perfusion experiments suggest Cl/HCO3 exchange at a rate of 8.6 meq/h (the sum of bicarbonate movements, 3.5 and 5.1 meq/h, observed in the two experiments) [29].
  • To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3 [30].
 

Gene context of carbonic acid

 

Analytical, diagnostic and therapeutic context of carbonic acid

  • Further, doubling the load from 250-500 pmol/min (by doubling the perfusion rate of 25-mM HCO3 solutions) did not stimulate JtCO2 in these normal animals [34].
  • In short-circuited bladders with the M pH lowered to the point of zero net H+ secretion, the rate of HCO3- entry into M in response to a 20-mM HCO3- gradient was measured by pH stat titration [35].
  • Gastrin-17 infusion did not inhibit gastric HCO3- secretion after vagotomy [36].
  • Whole-kidney and micropuncture measurements of GFR, FLHCO3, and whole-kidney and proximal tubule HCO3 reabsorption (APRHCO3) were coupled with BBMV measurements of H+ gradient-driven 22Na+ uptake in each animal studied [37].
  • Effect of proximal gastric vagotomy on calculated gastric HCO3- and nonparietal volume secretion in man. Studies during basal conditions and gastrin-17 infusion [36].

References

  1. Carbon dioxide transport and carbonic anhydrase in blood and muscle. Geers, C., Gros, G. Physiol. Rev. (2000) [Pubmed]
  2. Control of dynamic CFTR selectivity by glutamate and ATP in epithelial cells. Reddy, M.M., Quinton, P.M. Nature (2003) [Pubmed]
  3. Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis. Choi, J.Y., Muallem, D., Kiselyov, K., Lee, M.G., Thomas, P.J., Muallem, S. Nature (2001) [Pubmed]
  4. Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin. Schwartz, G.J., Tsuruoka, S., Vijayakumar, S., Petrovic, S., Mian, A., Al-Awqati, Q. J. Clin. Invest. (2002) [Pubmed]
  5. Load dependence of proximal tubular bicarbonate reabsorption in chronic metabolic alkalosis in the rat. Maddox, D.A., Gennari, F.J. J. Clin. Invest. (1986) [Pubmed]
  6. Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin. Flemström, G., Sjöblom, M., Jedstedt, G., Akerman, K.E. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  7. Effects of splanchnic nerve stimulation and of clonidine on gastric and duodenal HCO3- secretion in the anaesthetized cat. Fändriks, L., Jönson, C., Nylander, O. Acta Physiol. Scand. (1987) [Pubmed]
  8. The treatment of Kleine-Levin syndrome with lithium. Goldberg, M.A. Canadian journal of psychiatry. Revue canadienne de psychiatrie. (1983) [Pubmed]
  9. New spectrophotometric procedure for determining cefotaxime based on derivatization with 1,2-naphthoquinone-4-sulphonate into solid-phase extraction cartridges--application to pharmaceutical and urine samples. Martinez, L.G., Campíns-Falcó, P., Sevillano-Cabeza, A., Bosch-Reig, F. J. Chromatogr. B Biomed. Sci. Appl. (1998) [Pubmed]
  10. Gastroduodenal mucosal protection. Allen, A., Flemström, G., Garner, A., Kivilaakso, E. Physiol. Rev. (1993) [Pubmed]
  11. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Schultheis, P.J., Clarke, L.L., Meneton, P., Miller, M.L., Soleimani, M., Gawenis, L.R., Riddle, T.M., Duffy, J.J., Doetschman, T., Wang, T., Giebisch, G., Aronson, P.S., Lorenz, J.N., Shull, G.E. Nat. Genet. (1998) [Pubmed]
  12. Inhibition by anions of human red cell carbonic anhydrase B: physiological and biochemical implications. Maren, T.H., Rayburn, C.S., Liddell, N.E. Science (1976) [Pubmed]
  13. The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. Evidence that chronic hyponatremia is a potent stimulus to aldosterone secretion. Cohen, J.J., Hulter, H.N., Smithline, N., Melby, J.C., Schwartz, W.B. J. Clin. Invest. (1976) [Pubmed]
  14. Mineralocorticoids and acidosis regulate H+/HCO3- transport of intercalated cells. Kuwahara, M., Sasaki, S., Marumo, F. J. Clin. Invest. (1992) [Pubmed]
  15. Endotoxin impairs biliary glutathione and HCO3- excretion and blocks the choleretic effect of nitric oxide in rat liver. Trauner, M., Nathanson, M.H., Rydberg, S.A., Koeppel, T.A., Gartung, C., Sessa, W.C., Boyer, J.L. Hepatology (1997) [Pubmed]
  16. Alteration of Na+ homeostasis as a critical step in the development of irreversible hepatocyte injury after adenosine triphosphate depletion. Carini, R., Bellomo, G., Benedetti, A., Fulceri, R., Gamberucci, A., Parola, M., Dianzani, M.U., Albano, E. Hepatology (1995) [Pubmed]
  17. Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeleton. Southgate, C.D., Chishti, A.H., Mitchell, B., Yi, S.J., Palek, J. Nat. Genet. (1996) [Pubmed]
  18. Cell growth factors. Bicarbonate and pHi response. Thomas, R.C. Nature (1989) [Pubmed]
  19. Effect of secretion on intracellular pH regulation in isolated rat bile duct epithelial cells. Alvaro, D., Cho, W.K., Mennone, A., Boyer, J.L. J. Clin. Invest. (1993) [Pubmed]
  20. Na/H antiporter mRNA expression in single nephron segments of rat kidney cortex. Krapf, R., Solioz, M. J. Clin. Invest. (1991) [Pubmed]
  21. Intracellular pH regulation in rabbit renal medullary collecting duct cells. Role of chloride-bicarbonate exchange. Zeidel, M.L., Silva, P., Seifter, J.L. J. Clin. Invest. (1986) [Pubmed]
  22. Expression cloning and characterization of a renal electrogenic Na+/HCO3- cotransporter. Romero, M.F., Hediger, M.A., Boulpaep, E.L., Boron, W.F. Nature (1997) [Pubmed]
  23. Arginine vasopressin enhances pHi regulation in the presence of HCO3- by stimulating three acid-base transport systems. Ganz, M.B., Boyarsky, G., Sterzel, R.B., Boron, W.F. Nature (1989) [Pubmed]
  24. Plasticity of functional epithelial polarity. Schwartz, G.J., Barasch, J., Al-Awqati, Q. Nature (1985) [Pubmed]
  25. Rat hepatocytes exhibit basolateral Na+/HCO3- cotransport. Renner, E.L., Lake, J.R., Scharschmidt, B.F., Zimmerli, B., Meier, P.J. J. Clin. Invest. (1989) [Pubmed]
  26. cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. Smith, J.J., Welsh, M.J. J. Clin. Invest. (1992) [Pubmed]
  27. Cyclic adenosine monophosphate-stimulated anion transport in rabbit cortical collecting duct. Kinetics, stoichiometry, and conductive pathways. Schuster, V.L. J. Clin. Invest. (1986) [Pubmed]
  28. Mechanism of the ventilatory response to carbon monoxide. Santiago, T.V., Edelman, N.H. J. Clin. Invest. (1976) [Pubmed]
  29. Evaluation of chloride/bicarbonate. Exchange in the human colon in vivo. Davis, G.R., Morawski, S.G., Santa Ana, C.A., Fordtran, J.S. J. Clin. Invest. (1983) [Pubmed]
  30. Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback. Galla, J.H., Bonduris, D.N., Sanders, P.W., Luke, R.G. J. Clin. Invest. (1984) [Pubmed]
  31. Involvement of the anion exchanger SLC26A6 in prostaglandin E2- but not forskolin-stimulated duodenal HCO3- secretion. Tuo, B., Riederer, B., Wang, Z., Colledge, W.H., Soleimani, M., Seidler, U. Gastroenterology (2006) [Pubmed]
  32. Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO(3)(-) secretion: relevance to cystic fibrosis. Wang, Y., Soyombo, A.A., Shcheynikov, N., Zeng, W., Dorwart, M., Marino, C.R., Thomas, P.J., Muallem, S. EMBO J. (2006) [Pubmed]
  33. A gene homologous to the subunit-2 gene of NADH dehydrogenase is essential to inorganic carbon transport of Synechocystis PCC6803. Ogawa, T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  34. An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats. Levine, D.Z. J. Clin. Invest. (1985) [Pubmed]
  35. Energy dependence of urinary bicarbonate secretion in turtle bladder. Oliver, J.A., Himmelstein, S., Steinmetz, P.R. J. Clin. Invest. (1975) [Pubmed]
  36. Effect of proximal gastric vagotomy on calculated gastric HCO3- and nonparietal volume secretion in man. Studies during basal conditions and gastrin-17 infusion. Feldman, M., Blair, A.J., Richardson, C.T. J. Clin. Invest. (1987) [Pubmed]
  37. Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex. Maddox, D.A., Fortin, S.M., Tartini, A., Barnes, W.D., Gennari, F.J. J. Clin. Invest. (1992) [Pubmed]
 
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