Holecistokininski receptor B

Holecistokininski receptor B
NMR struktura treće ektracelularne petlje humanog CCK-B receptora. PDB prikaz baziran na 1l4t​.
Dostupne strukture
1l4t​
Identifikatori
Simboli CCKBR; CCK-B; GASR
Vanjski ID OMIM: 118445 MGI: 99479 HomoloGene: 7258 IUPHAR: CCK2 GeneCards: CCKBR Gene
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 887 12426
Ensembl ENSG00000110148 ENSMUSG00000030898
UniProt P32239 Q3ZB46
RefSeq (mRNA) NM_176875 NM_007627
RefSeq (protein) NP_795344 NP_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

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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.[8][12] 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]

== Selektivni ligandi ==

Agonisti

Antagonisti

  • Proglumid
  • CI-988
  • CI-1015
  • L-365,260
  • L-369,293
  • YF-476
  • YM-022
  • RP-69758
  • LY-225,910
  • LY-288,513
  • PD-135,158
  • PD-145,942

Inverzni agonist

  • L-740,093

Vidi još

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Reference

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  1. ^ Noble F, Roques BP (1999). „CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology”. Prog. Neurobiol. 58 (4): 349—79. PMID 10368033. doi:10.1016/S0301-0082(98)00090-2. 
  2. ^ Pisegna JR, de Weerth A, Huppi K, Wank SA (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. PMID 1280419. doi:10.1016/0006-291X(92)91557-7. 
  3. ^ Harikumar KG, Clain J, Pinon DI, Dong M, Miller LJ (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. PMID 15520004. doi:10.1074/jbc.M409480200. 
  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 (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 (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. PMID 12695525. doi:10.1124/mol.63.5.973. 
  6. ^ „Entrez Gene: CCKBR cholecystokinin B receptor”. 
  7. ^ Altar CA, Boyar WC (1989). „Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin”. Brain Res. 483 (2): 321—6. PMID 2706523. doi:10.1016/0006-8993(89)90176-5. 
  8. ^ а б Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (2003). „Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum”. Life Sci. 73 (6): 727—39. PMID 12801594. doi:10.1016/S0024-3205(03)00393-X. 
  9. ^ Lanza M, Makovec F (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. PMID 10651144. doi:10.1007/s002109900161. 
  10. ^ Dourish CT, O'Neill MF, Coughlan J, Kitchener SJ, Hawley D, Iversen SD (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. PMID 2311658. doi:10.1016/0014-2999(90)90129-T. 
  11. ^ Higgins GA, Sills TL, Tomkins DM, Sellers EM, Vaccarino FJ (1994). „Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion”. Pharmacol. Biochem. Behav. 48 (4): 1019—24. PMID 7972279. doi:10.1016/0091-3057(94)90214-3. 
  12. ^ Lu L, Huang M, Ma L, Li J (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. PMID 11173090. doi:10.1016/S0166-4328(00)00361-2. 
  13. ^ Boyce S, Rupniak NM, Tye S, Steventon MJ, Iversen SD (1990). „Modulatory role for CCK-B antagonists in Parkinson's disease”. Clin Neuropharmacol. 13 (4): 339—47. PMID 1976438. doi:10.1097/00002826-199008000-00009. 

Literatura

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  • 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. PMID 8343165. doi:10.1006/bbrc.1993.1894. 
  • 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. 
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