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 IDOMIM: 118445 MGI: 99479 HomoloGene: 7258 IUPHAR: CCK2 GeneCards: CCKBR Gene
Ontologija gena
Molekularna funkcija aktivnost rodopsinu-sličnog receptora
aktivnost fosfoinozitid fosfolipaze C
receptorska aktivnost
aktivnost gastrinskog receptora
aktivnost regulatora fosfatidilinozitol 3-kinaze
Celularna komponenta ćelijska membrana
integralno sa ćelijskom membranom
Biološki proces aktivacija fosfolipaze C
elevacija koncentracije citozolnih jona kalcijuma
varenje
senzorna percepcija
način ishrane
ćelijska proliferacija
pozitivna regulacija ćelijske proliferacije
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

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]

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Reference

  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

  • 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. 
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PDB Galerija
1l4t: Rešenje NMR strukture CCK2E3
1l4t: Rešenje NMR strukture CCK2E3  
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Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Neuropeptidni receptori
Hormonski receptori
Drugi
Opioidni receptori
Drugi neuropeptidni receptori
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Holecistokinin
CCKA
Agonisti: Holecistokinin • CCK-4
Antagonisti: Asperlicin • Proglumid • Lorglumid • Devazepid • Deksloksiglumid
CCKB
Agonisti: Holecistokinin • CCK-4 • Gastrin
Antagonisti: Proglumid • CI-988
CRH
CRF1
CRF2
Galanin
GAL1
Agonisti: Galanin • Galaninu-sličan peptid • Galmic • Galnon
GAL2
Agonisti: Galanin • Galaninu-sličan peptid • Galmic • Galnon
GAL3
Agonisti: Galanin • Galmic • Galnon
Grelin
Agonisti: Grelin • Kapromorelin • MK-677 • Sermorelin • SM-130,686 • Tabimorelin
MCH
MCH1
MCH2
Melanokortin
MC1
MC2
Agonisti: ACTH • Kosintropin • Tetrakosaktid
MC3
Agonisti: alfa-MSH • Bremelanotid • Melanotan II
MC4
Agonisti: alfa-MSH • Bremelanotid • Melanotan II • THIQ
Antagonisti: Agutiju srodni peptid
MC5
Agonisti: alfa-MSH • Melanotan II
Neuropeptid S
Agonisti: Neuropeptid S
Antagonisti: SHA-68
Neuropeptid Y
Y1
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: BIBP-3226
Y2
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: BIIE-0246
Y4
Agonisti: Neuropeptid Y • Pankreasni polipeptid • Peptid YY
Antagonisti: UR-AK49
Y5
Agonisti: Neuropeptid Y • Peptid YY
Antagonisti: Lu AA-33810
Neurotenzin
NTS1
Agonisti: Neurotenzin • Neuromedin N
Antagonisti: SR-48692 • SR-142,948
NTS2
Agonisti: Neurotenzin
Antagonisti: Levokabastin • SR-142,948
Opioid
vidi Opioidi
Oreksin
OX1
Agonisti: Oreksin-A
Antagonisti: Almoreksant • SB-334,867 • SB-408,124 • SB-649,868
OX2
Agonisti: Oreksin-A
Antagonisti: Almoreksant • SB-649,868 • TCS-OX2-29
Oksitocin
Agonisti: Karbetocin • Demoksitocin • Oksitocin • WAY-267,464
Antagonisti: Atosiban • L-371,257 • L-368,899
Tahikinin
NK1
Agonisti: Supstanca P
Antagonisti: Aprepitant • Befetupitant • Kasopitant • CI-1021 • CP-96,345 • CP-99,994 • CP-122,721 • Dapitant • Ezlopitant • FK-888 • Fosaprepitant • GR-203,040 • GW-597,599 • HSP-117 • L-733,060 • L-741,671 • L-743,310 • L-758,298 • Lanepitant • LY-306,740 • Maropitant • Netupitant • NKP-608 • Nolpitantium • Orvepitant • RP-67,580 • SDZ NKT 343 • Vestipitant • Vofopitant
NK2
Agonisti: Neurokinin A
Antagonisti: GR-159897 • Ibodutant • Saredutant
NK3
Agonisti: Neurokinin B
Antagonisti: Osanetant • Talnetant
Vazopresin
V1A
Agonisti: Dezmopresin • Felipresin • Ornipresin • Terlipresin • Vazopresin
Antagonisti: Konivaptan • Demeklociklin • Relkovaptan
V1B
Agonisti: Felipresin • Ornipresin • Terlipresin • Vazopresin
Antagonisti: Demeklociklin • Nelivaptan
V2
Agonisti: Dezmopresin • Ornipresin • Vazopresin
Antagonisti: Konivaptan • Demeklociklin • Liksivaptan • Mozavaptan • Satavaptan • Tolvaptan