Holecistokininski receptor B

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Holecistokininski receptor B

NMR struktura treće ektracelularne petlje humanog CCK-B receptora. PDB prikaz baziran na 1l4t.
Dostupne strukture
1l4t
Identifikatori
SimboliCCKBR; CCK-B; GASR
Vanjski IDOMIM118445 MGI99479 HomoloGene7258 IUPHAR: CCK2 GeneCards: CCKBR Gene
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez88712426
EnsemblENSG00000110148ENSMUSG00000030898
UniProtP32239Q3ZB46
RefSeq (mRNA)NM_176875NM_007627
RefSeq (protein)NP_795344NP_031653
Lokacija (UCSC)Chr 11:
6.24 - 6.25 Mb
Chr 7:
105.3 - 105.34 Mb
PubMed pretraga[1][2]

Holecistokininski receptor B (CCKBR ili CCK2) je protein[1] koji je kod ljudi kodiran CCKBR genom.[2]

Ovaj gen kodira G protein-spregnuti receptor za gastrin i holecistokinin (CCK),[3][4][5] regulatorne peptide mozga i gastrointestinalnog trakta. On je gastrinski receptor tipa B, koji ima visok afinitet za sulfonovane i nesulfonovane CCK analoge. Pogrešno splajsovane transkriptne varijante su primećene u tumorima debelog creva i gušterače.[6]

CNS dejstvo[uredi | uredi kod]

CCK receptori imaju znatan uticaj na neurotransmisiju u mozgu, regulaciju anksioznosti, unos hrane, i lokomociju. CCK-B izražavanje ima uticaja na anksiozne i depreesivne fenotipe ljudi. CCK-B receptori uzimaju udela u kompleksnoj regulaciji dopamina u mozgu. CCK-B aktivacija ima inhibitorno dejstvo na dopaminsku aktivnost, ona suzbija dopaminom pojačane efekte CCK-A receptora. Međutim ova interakcija CCKB-a i dopamina je veoma zavisna od lokacije.[7] CCK-B antagonizam uvećava dopaminsko oslobađanje u strijatumu pacova.[8] Aktivacija povećava GABA oslobađanje unutar nucleus accumbens septi pacova.[9] CCK-B receptori moduliraju dopaminsko oslobađanje, i utiču na razvoj tolerancije na opioide.[10] CCK-B aktivacija umanjuje amfetaminom indukovano DA oslobađanje, i doprinosi individualnoj varijabilnosti responsa na amfetamin.[11]

Kod pacova, CCK-B antagonizam sprečava stresom podstaknutu reaktivaciju kokainske zavisnoti, kao i dugotrajno održavanje i ponovno uspostavljanje morfinske zavisnosti.[12][8] Smatra se da CCK-B ima modulatornu ulogu u Parkinsonovoj bolesti. Blokada CCK-B kod Sajmirskih majmuna sa sniženim nivoom dopamina uzrokuje znatno povišenje lokomotornog L-DOPA responsa.[13]

2

Vidi još[uredi | uredi kod]

Reference[uredi | uredi kod]

  1. Noble F, Roques BP (July 1999). „CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology”. Prog. Neurobiol. 58 (4): 349–79. DOI:10.1016/S0301-0082(98)00090-2. PMID 10368033. 
  2. Pisegna JR, de Weerth A, Huppi K, Wank SA (November 1992). „Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization”. Biochem. Biophys. Res. Commun. 189 (1): 296–303. DOI:10.1016/0006-291X(92)91557-7. PMID 1280419. 
  3. Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (January 2005). „Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy”. J. Biol. Chem. 280 (2): 1044–50. DOI:10.1074/jbc.M409480200. PMID 15520004. 
  4. Aloj L, Caracò C, Panico M, Zannetti A, Del Vecchio S, Tesauro D, De Luca S, Arra C, Pedone C, Morelli G, Salvatore M (March 2004). „In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging”. J. Nucl. Med. 45 (3): 485–94. PMID 15001692. 
  5. Galés C, Poirot M, Taillefer J, Maigret B, Martinez J, Moroder L, Escrieut C, Pradayrol L, Fourmy D, Silvente-Poirot S (May 2003). „Identification of tyrosine 189 and asparagine 358 of the cholecystokinin 2 receptor in direct interaction with the crucial C-terminal amide of cholecystokinin by molecular modeling, site-directed mutagenesis, and structure/affinity studies”. Mol. Pharmacol. 63 (5): 973–82. DOI:10.1124/mol.63.5.973. PMID 12695525. 
  6. „Entrez Gene: CCKBR cholecystokinin B receptor”. 
  7. Altar CA, Boyar WC (April 1989). „Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin”. Brain Res. 483 (2): 321–6. DOI:10.1016/0006-8993(89)90176-5. PMID 2706523. 
  8. 8,0 8,1 Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (June 2003). „Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum”. Life Sci. 73 (6): 727–39. DOI:10.1016/S0024-3205(03)00393-X. PMID 12801594. 
  9. Lanza M, Makovec F (January 2000). „Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons”. Naunyn Schmiedebergs Arch. Pharmacol. 361 (1): 33–8. DOI:10.1007/s002109900161. PMID 10651144. 
  10. Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (January 1990). „The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat”. Eur. J. Pharmacol. 176 (1): 35–44. DOI:10.1016/0014-2999(90)90129-T. PMID 2311658. 
  11. Higgins GA, Sills TL, Tomkins DM, Sellers EM, Vaccarino FJ (August 1994). „Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion”. Pharmacol. Biochem. Behav. 48 (4): 1019–24. DOI:10.1016/0091-3057(94)90214-3. PMID 7972279. 
  12. Lu L, Huang M, Ma L, Li J (April 2001). „Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats”. Behav. Brain Res. 120 (1): 105–10. DOI:10.1016/S0166-4328(00)00361-2. PMID 11173090. 
  13. Boyce S, Rupniak NM, Tye S, Steventon MJ, Iversen SD (August 1990). „Modulatory role for CCK-B antagonists in Parkinson's disease”. Clin Neuropharmacol 13 (4): 339–47. DOI:10.1097/00002826-199008000-00009. PMID 1976438. 

Literatura[uredi | uredi kod]

  • Herget T, Sethi T, Wu SV, et al. (1994). „Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors.”. Ann. N. Y. Acad. Sci. 713: 283–97. DOI:10.1111/j.1749-6632.1994.tb44076.x. PMID 8185170. 
  • Lee YM, Beinborn M, McBride EW, et al. (1993). „The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization.”. J. Biol. Chem. 268 (11): 8164–9. PMID 7681836. 
  • Ito M, Iwata N, Taniguchi T, et al. (1995). „Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene.”. Cell Growth Differ. 5 (10): 1127–35. PMID 7848914. 
  • Miyake A (1995). „A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon.”. Biochem. Biophys. Res. Commun. 208 (1): 230–7. DOI:10.1006/bbrc.1995.1328. PMID 7887934. 
  • Maruyama K, Sugano S (1994). „Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.”. Gene 138 (1-2): 171–4. DOI:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Zimonjic DB, Popescu NC, Matsui T, et al. (1993). „Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5→p15.4 by fluorescence in situ hybridization.”. Cytogenet. Cell Genet. 65 (3): 184–5. DOI:10.1159/000133628. PMID 8222757. 
  • de Weerth A, Pisegna JR, Huppi K, Wank SA (1993). „Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor.”. Biochem. Biophys. Res. Commun. 194 (2): 811–8. DOI:10.1006/bbrc.1993.1894. PMID 8343165. 
  • Ito M, Matsui T, Taniguchi T, et al. (1993). „Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin.”. J. Biol. Chem. 268 (24): 18300–5. PMID 8349705. 
  • Song I, Brown DR, Wiltshire RN, et al. (1993). „The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs.”. Proc. Natl. Acad. Sci. U.S.A. 90 (19): 9085–9. DOI:10.1073/pnas.90.19.9085. PMC 47506. PMID 8415658. 
  • Beinborn M, Lee YM, McBride EW, et al. (1993). „A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists.”. Nature 362 (6418): 348–50. DOI:10.1038/362348a0. PMID 8455720. 
  • Silvente-Poirot S, Wank SA (1996). „A segment of five amino acids in the second extracellular loop of the cholecystokinin-B receptor is essential for selectivity of the peptide agonist gastrin.”. J. Biol. Chem. 271 (25): 14698–706. DOI:10.1074/jbc.271.25.14698. PMID 8663021. 
  • Tarasova NI, Wank SA, Hudson EA, et al. (1997). „Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor.”. Cell Tissue Res. 287 (2): 325–33. DOI:10.1007/s004410050757. PMID 8995203. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). „Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.”. Gene 200 (1-2): 149–56. DOI:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • O'Briant KC, Ali SY, Weier HU, Bepler G (1999). „An 84-kilobase physical map and repeat polymorphisms of the gastrin/cholecystokinin brain receptor region at the junction of chromosome segments 11p15.4 and 15.5.”. Chromosome Res. 6 (5): 415–8. DOI:10.1023/A:1009289625352. PMID 9872672. 
  • Monstein HJ, Nilsson I, Ellnebo-Svedlund K, Svensson SP (1999). „Cloning and characterization of 5'-end alternatively spliced human cholecystokinin-B receptor mRNAs.”. Recept. Channels 6 (3): 165–77. PMID 10100325. 
  • Daulhac L, Kowalski-Chauvel A, Pradayrol L, et al. (1999). „Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors.”. J. Biol. Chem. 274 (29): 20657–63. DOI:10.1074/jbc.274.29.20657. PMID 10400698. 
  • Silvente-Poirot S, Escrieut C, Galès C, et al. (1999). „Evidence for a direct interaction between the penultimate aspartic acid of cholecystokinin and histidine 207, located in the second extracellular loop of the cholecystokinin B receptor.”. J. Biol. Chem. 274 (33): 23191–7. DOI:10.1074/jbc.274.33.23191. PMID 10438490. 
  • Kulaksiz H, Arnold R, Göke B, et al. (2000). „Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach.”. Cell Tissue Res. 299 (2): 289–98. DOI:10.1007/s004410050027. PMID 10741470.