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Gene Review

Abcc8  -  ATP-binding cassette, subfamily C...

Rattus norvegicus

Synonyms: ATP-binding cassette sub-family C member 8, Sulfonylurea receptor 1, Sur, Sur1
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Disease relevance of Abcc8


High impact information on Abcc8

  • RESULTS: Stimulation of cholangiocyte secretion by glibenclamide and tolbutamide required Cl - and was mediated by the sulfonylurea receptor 2B [7].
  • To determine the interaction site(s) of ATP-sensitive K(+) (K(ATP)) channels for G-proteins, sulfonylurea receptor (SUR2A or SUR1) and pore-forming (Kir6.2) subunits were reconstituted in the mammalian cell line, COS-7 [8].
  • This effect involved specific interactions between MgADP and SUR, as it required Mg(2+), but not ATP, and was abolished by point mutations in the second nucleotide-binding domain of SUR, which impaired channel activation by MgADP [9].
  • The pharmacological phenotype of ATP-sensitive potassium (K(ATP)) channels is defined by their tissue-specific regulatory subunit, the sulfonylurea receptor (SUR), which associates with the pore-forming channel core, Kir6 [9].
  • We have suggested that holo-mitoK(ATP) is a heteromultimer consisting of an inwardly rectifying K(+) channel (mitoKIR) and a sulfonylurea receptor (Grover, G. J., and Garlid, K. D. (2000) J. Mol. Cell. Cardiol. 32, 677-695) [10].

Chemical compound and disease context of Abcc8

  • From these data, we conclude that sulfonylurea receptors develop mostly in the first 2 wk postnatally and chronic hypoxia increases sulfonylurea receptor expression in utero in spite of the fact that overall protein decreases [2].

Biological context of Abcc8


Anatomical context of Abcc8


Associations of Abcc8 with chemical compounds

  • ATP-regulated (K(ATP)) channels are formed by an inward rectifier pore-forming subunit (Kir) and a sulfonylurea (glibenclamide)-binding protein, a member of the ATP binding cassette family (sulfonylurea receptor (SUR) or cystic fibrosis transmembrane conductance regulator) [19].
  • RT-PCR revealed that nicorandil increased the eNOS and SUR2 mRNA levels by 2.2- and 2.0-fold, respectively, (p < 0.01 versus control), and that these increases were completely inhibited by glibenclamide [20].
  • The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures) [21].
  • Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold [22].
  • The third transmembrane domain of SUR is found to be an important determinant of the response to cromakalim, which possibly harbors at least part of its binding site [23].

Other interactions of Abcc8


Analytical, diagnostic and therapeutic context of Abcc8


  1. Modulation of the trafficking efficiency and functional properties of ATP-sensitive potassium channels through a single amino acid in the sulfonylurea receptor. Cartier, E.A., Shen, S., Shyng, S.L. J. Biol. Chem. (2003) [Pubmed]
  2. Sulfonylurea receptor expression in rat brain: effect of chronic hypoxia during development. Xia, Y., Eisenman, D., Haddad, G.G. Pediatr. Res. (1993) [Pubmed]
  3. Direct photoaffinity labeling of the putative sulfonylurea receptor in rat beta-cell tumor membranes by [3H]glibenclamide. Kramer, W., Oekonomopulos, R., Pünter, J., Summ, H.D. FEBS Lett. (1988) [Pubmed]
  4. Molecular structure of the glibenclamide binding site of the beta-cell K(ATP) channel. Mikhailov, M.V., Mikhailova, E.A., Ashcroft, S.J. FEBS Lett. (2001) [Pubmed]
  5. Differential interaction of glimepiride and glibenclamide with the beta-cell sulfonylurea receptor. I. Binding characteristics. Müller, G., Hartz, D., Pünter, J., Okonomopulos, R., Kramer, W. Biochim. Biophys. Acta (1994) [Pubmed]
  6. Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Simard, J.M., Chen, M., Tarasov, K.V., Bhatta, S., Ivanova, S., Melnitchenko, L., Tsymbalyuk, N., West, G.A., Gerzanich, V. Nat. Med. (2006) [Pubmed]
  7. Glibenclamide stimulates fluid secretion in rodent cholangiocytes through a cystic fibrosis transmembrane conductance regulator-independent mechanism. Spirlì, C., Fiorotto, R., Song, L., Santos-Sacchi, J., Okolicsanyi, L., Masier, S., Rocchi, L., Vairetti, M.P., De Bernard, M., Melero, S., Pozzan, T., Strazzabosco, M. Gastroenterology (2005) [Pubmed]
  8. A region of the sulfonylurea receptor critical for a modulation of ATP-sensitive K(+) channels by G-protein betagamma-subunits. Wada, Y., Yamashita, T., Imai, K., Miura, R., Takao, K., Nishi, M., Takeshima, H., Asano, T., Morishita, R., Nishizawa, K., Kokubun, S., Nukada, T. EMBO J. (2000) [Pubmed]
  9. Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. D'hahan, N., Moreau, C., Prost, A.L., Jacquet, H., Alekseev, A.E., Terzic, A., Vivaudou, M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. Functional distinctions between the mitochondrial ATP-dependent K+ channel (mitoKATP) and its inward rectifier subunit (mitoKIR). Mironova, G.D., Negoda, A.E., Marinov, B.S., Paucek, P., Costa, A.D., Grigoriev, S.M., Skarga, Y.Y., Garlid, K.D. J. Biol. Chem. (2004) [Pubmed]
  11. The high-affinity sulfonylurea receptor: distribution, glycosylation, purification, and immunoprecipitation of two forms from endocrine and neuroendocrine cell lines. Nelson, D.A., Bryan, J., Wechsler, S., Clement, J.P., Aguilar-Bryan, L. Biochemistry (1996) [Pubmed]
  12. Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances known. Straub, S.G., Mulvaney-Musa, J., Yajima, H., Weiland, G.A., Sharp, G.W. Diabetes (2003) [Pubmed]
  13. The binding properties of the particulate and solubilized sulfonylurea receptor from cerebral cortex are modulated by the Mg2+ complex of ATP. Schwanstecher, M., Schaupp, U., Löser, S., Panten, U. J. Neurochem. (1992) [Pubmed]
  14. Effects of sulfonylureas, alpha-endosulfine counterparts, on glomerulosclerosis in type 1 and type 2 models of diabetes. Biederman, J.I., Vera, E., Rankhaniya, R., Hassett, C., Giannico, G., Yee, J., Cortes, P. Kidney Int. (2005) [Pubmed]
  15. Short-term intermittent exposure to diazoxide improves functional performance of beta-cells in a high-glucose environment. Yoshikawa, H., Ma, Z., Björklund, A., Grill, V. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  16. Rat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevis oocyte. Tanemoto, M., Vanoye, C.G., Dong, K., Welch, R., Abe, T., Hebert, S.C., Xu, J.Z. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  17. Evidence for presence of ATP-sensitive K+ channels in rat colonic smooth muscle cells. Plujà, L., Yokoshiki, H., Sperelakis, N. Can. J. Physiol. Pharmacol. (1998) [Pubmed]
  18. Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel. Ashfield, R., Gribble, F.M., Ashcroft, S.J., Ashcroft, F.M. Diabetes (1999) [Pubmed]
  19. An amino acid triplet in the NH2 terminus of rat ROMK1 determines interaction with SUR2B. Dong, K., Xu, J., Vanoye, C.G., Welch, R., MacGregor, G.G., Giebisch, G., Hebert, S.C. J. Biol. Chem. (2001) [Pubmed]
  20. Nicorandil enhances cardiac endothelial nitric oxide synthase expression via activation of adenosine triphosphate-sensitive K channel in rat. Horinaka, S., Kobayashi, N., Higashi, T., Hara, K., Hara, S., Matsuoka, H. J. Cardiovasc. Pharmacol. (2001) [Pubmed]
  21. PIP2 and ATP cooperatively prevent cytosolic Ca2+-induced modification of ATP-sensitive K+ channels in rat pancreatic beta-cells. Koriyama, N., Kakei, M., Nakazaki, M., Yaekura, K., Ichinari, K., Gong, Q., Morimitsu, S., Yada, T., Tei, C. Diabetes (2000) [Pubmed]
  22. Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. Gribble, F.M., Proks, P., Corkey, B.E., Ashcroft, F.M. J. Biol. Chem. (1998) [Pubmed]
  23. A transmembrane domain of the sulfonylurea receptor mediates activation of ATP-sensitive K(+) channels by K(+) channel openers. D'hahan, N., Jacquet, H., Moreau, C., Catty, P., Vivaudou, M. Mol. Pharmacol. (1999) [Pubmed]
  24. Pore-forming subunits of K-ATP channels, Kir6.1 and Kir6.2, display prominent differences in regional and cellular distribution in the rat brain. Thomzig, A., Laube, G., Prüss, H., Veh, R.W. J. Comp. Neurol. (2005) [Pubmed]
  25. Impact of in vivo preconditioning by isoflurane on adenosine triphosphate-sensitive potassium channels in the rat heart: lasting modulation of nucleotide sensitivity during early memory period. Stadnicka, A., Marinovic, J., Bienengraeber, M., Bosnjak, Z.J. Anesthesiology (2006) [Pubmed]
  26. The mitochondrial sulfonylurea receptor: identification and characterization. Szewczyk, A., Wójcik, G., Lobanov, N.A., Nałecz, M.J. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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