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Gene Review

Car4  -  carbonic anhydrase 4

Rattus norvegicus

Synonyms: CA-IV, Ca4, Carbonate dehydratase IV, Carbonic anhydrase 4, Carbonic anhydrase IV
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Disease relevance of Ca4

  • CONCLUSIONS: Vascular mineral loss induced by the blockade of endothelin receptors seems dependent on the activation of membrane-bound CA IV, suggesting that mineral loss may proceed via local changes in pH similar to that seen in bone resorption [1].

High impact information on Ca4

  • Thus, the distribution of CA IV is quite distinct from that of CA II; it corresponds with the localization of an isoenzyme(s) that did not stain with antibodies against CA II but that was revealed by histochemical-staining procedures [2].
  • CA IV was localized in apical plasma membranes of the proximal convoluted tubule and the thick ascending limb of Henle [2].
  • We conclude that the apical CA IV is the luminal CA responsible for bicarbonate reabsorption in the proximal tubule and the thick ascending limb in the rat kidney [2].
  • These studies also suggest that CA IV plays a role in bicarbonate transport across the basolateral plasma membrane in these two segments of the rat nephron [2].
  • Rat lung CA IV was found to be relatively resistant to sodium dodecyl sulfate and to be anchored to membranes by a phosphatidylinositol-glycan linkage; both properties were found to be shared by other mammalian CA IVs [3].

Biological context of Ca4


Anatomical context of Ca4


Associations of Ca4 with chemical compounds

  • Moreover, CA IV immunostaining was enhanced much later in the carotids, where darusentan did not cause regression of elastocalcinosis [1].
  • Calcium phosphate cement (CPC) consisting of Ca4 (PO4)2O and CaHPO4 (2H2O) was recently developed [10].
  • The inhibition produced by PIPLC or CA IV antisera was not significantly less than that by benzolamide, suggesting that the majority of detectable surface CA activity was attributable to CA IV [8].
  • In the present study, we examined the expression and androgen regulation of CA IV and II mRNAs along the epididymal duct [9].
  • Peak effect was reached with 100 mg/kg, eliciting 40 mM HCO3- in urine; this is taken to be the effect of inhibiting CA IV [11].

Physical interactions of Ca4

  • It is further concluded that the cytosolic carbonic anhydrase (CA II) and the membrane-bound carbonic anhydrase (CA IV) are not involved in glucose synthesis from pyruvate [12].

Other interactions of Ca4

  • Here it was found that TpOH-ir neurones in the medullary raphe were immunoreactive for carbonic anhydrase type II and type IV (CA II and CA IV) [13].
  • Western blot analysis using isozyme-specific antisera indicated that astrocytes contain CA II, a cytosolic isozyme, but CA III, CA IV and CA V could not be detected [14].

Analytical, diagnostic and therapeutic context of Ca4


  1. Regression of medial elastocalcinosis in rat aorta: a new vascular function for carbonic anhydrase. Essalihi, R., Dao, H.H., Gilbert, L.A., Bouvet, C., Semerjian, Y., McKee, M.D., Moreau, P. Circulation (2005) [Pubmed]
  2. Localization of membrane-associated carbonic anhydrase type IV in kidney epithelial cells. Brown, D., Zhu, X.L., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Membrane-associated carbonic anhydrase from rat lung. Purification, characterization, tissue distribution, and comparison with carbonic anhydrase IVs of other mammals. Waheed, A., Zhu, X.L., Sly, W.S. J. Biol. Chem. (1992) [Pubmed]
  4. Pulmonary carbonic anhydrase IV: developmental regulation and cell-specific expression in the capillary endothelium. Fleming, R.E., Crouch, E.C., Ruzicka, C.A., Sly, W.S. Am. J. Physiol. (1993) [Pubmed]
  5. Membrane-associated carbonic anhydrase IV in skeletal muscle: subcellular localization. Decker, B., Sender, S., Gros, G. Histochem. Cell Biol. (1996) [Pubmed]
  6. Cysteamine, the most potent ulcerogenic drug known so far, powerfully activates carbonic anhydrase I, II and IV. In vitro and in vivo studies. Puscas, I., Coltau, M., Maghiar, A., Domuta, G. Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. (2000) [Pubmed]
  7. Rat embryos express transcripts for cyclooxygenase-1 and carbonic anhydrase-4, but not for cyclooxygenase-2, during organogenesis. Streck, R.D., Kumpf, S.W., Ozolins, T.R., Stedman, D.B. Birth Defects Res. B Dev. Reprod. Toxicol. (2003) [Pubmed]
  8. Functional demonstration of surface carbonic anhydrase IV activity on rat astrocytes. Svichar, N., Esquenazi, S., Waheed, A., Sly, W.S., Chesler, M. Glia (2006) [Pubmed]
  9. Regional expression and androgen regulation of carbonic anhydrase IV and II in the adult rat epididymis. Kaunisto, K., Fleming, R.E., Kneer, J., Sly, W.S., Rajaniemi, H. Biol. Reprod. (1999) [Pubmed]
  10. Histopathological reactions of calcium phosphate cement. Sugawara, A., Nishiyama, M., Kusama, K., Moro, I., Nishimura, S., Kudo, I., Chow, L.C., Takagi, S. Dental materials journal. (1992) [Pubmed]
  11. Renal and cerebrospinal fluid formation pharmacology of a high molecular weight carbonic anhydrase inhibitor. Maren, T.H., Conroy, C.W., Wynns, G.C., Godman, D.R. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  12. Mitochondrial carbonic anhydrase is involved in rat renal glucose synthesis. Dodgson, S.J., Cherian, K. Am. J. Physiol. (1989) [Pubmed]
  13. Quantification of the response of rat medullary raphe neurones to independent changes in pH(o) and P(CO2). Wang, W., Bradley, S.R., Richerson, G.B. J. Physiol. (Lond.) (2002) [Pubmed]
  14. Effect of carbonic anhydrase inhibition and acetoacetate on anaplerotic pyruvate carboxylase activity in cultured rat astrocytes. Hazen, S.A., Waheed, A., Sly, W.S., LaNoue, K.F., Lynch, C.J. Dev. Neurosci. (1997) [Pubmed]
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