Reseptor kolesistokinin B

CCKBR
Struktur yang tersedia PDB Pencarian Ortolog: PDBe RCSB Daftar kode id PDB 1L4T
Pengidentifikasi
Alias	CCKBR, CCK-B, CCK2R, GASR, cholecystokinin B receptor
ID eksternal	OMIM: 118445 MGI: 99479 HomoloGene: 7258 GeneCards: CCKBR
Lokasi gen (Manusia) Kr. Kromosom 11 (manusia)[1] Pita 11p15.4 Awal 6,259,806 bp[1] Akhir 6,272,127 bp[1]
Lokasi gen (Tikus) Kr. Kromosom 7 (tikus)[2] Pita 7 E3|7 55.86 cM Awal 105,074,938 bp[2] Akhir 105,120,105 bp[2]
Pola ekspresi RNA Referensi data ekspresi selengkapnya
Ontologi gen Fungsi molekuler • G protein-coupled receptor activity • signal transducer activity • 1-phosphatidylinositol-3-kinase regulator activity • GO:0001948, GO:0016582 Ikatan protein plasma • type B gastrin/cholecystokinin receptor binding • gastrin receptor activity • cholecystokinin receptor activity • peptide hormone binding Komponen seluler • komponen integral membran • membran • Membran sel Proses biologis • gastric acid secretion • positive regulation of cytosolic calcium ion concentration • cell surface receptor signaling pathway • positive regulation of cell population proliferation • cell population proliferation • digestive tract development • GO:0072468 signal transduction • gland development • regulation of phosphatidylinositol 3-kinase activity • G protein-coupled receptor signaling pathway • phospholipase C-activating G protein-coupled receptor signaling pathway • cholecystokinin signaling pathway • pH reduction Sumber:Amigo / QuickGO
Ortolog
Spesies	Manusia	Tikus
Entrez	887	12426
Ensembl	ENSG00000110148	ENSMUSG00000030898
UniProt	P32239	P56481
RefSeq (mRNA)	NM_176875 NM_001318029 NM_001363552	NM_007627
RefSeq (protein)	NP_001304958 NP_795344 NP_001350481	NP_031653
Lokasi (UCSC)	Chr 11: 6.26 – 6.27 Mb	Chr 7: 105.07 – 105.12 Mb
Pencarian PubMed	[3]	[4]
Wikidata
Lihat/Sunting Manusia Lihat/Sunting Tikus

Reseptor kolesistokinin B juga dikenal sebagai CCKBR atau CCK₂ adalah protein[5] yang pada manusia disandikan oleh gen CCKBR.[6]

Gen ini menyandi reseptor terhubung protein G untuk gastrin dan kolesistokinin (CCK),[7][8][9] yang merupakan suatu peptida pengatur otak dan saluran pencernaan. Protein ini adalah reseptor gastrin tipe B, yang memiliki afinitas tinggi untuk analog CCK yang tersulfatasi dan nonsulfatasi, ditemukan terutama dalam sistem saraf pusat dan saluran pencernaan. Varian transkrip salah potong termasuk intron telah diamati dalam sel-sel dari tumor kolorektal dan pankreas.[10]

Efek pada sistem saraf pusat

Reseptor CCK secara signifikan memengaruhi transmisi saraf di otak, mengatur kecemasan, makan, dan lokomosi. Ekspresi CCK-B dapat berkorelasi paralel dengan fenotipe kecemasan dan depresi pada manusia. Reseptor CCK-B memiliki regulasi aktivitas dopamin yang kompleks di otak. Aktivasi CCK-B tampaknya memiliki aksi penghambatan umum pada aktivitas dopamin di otak, menentang efek peningkatan-dopamin dari CCK-A. Namun, efek CCK-B pada aktivitas dopamin bervariasi tergantung pada lokasi.[11] Antagonisme CCK-B meningkatkan pelepasan dopamin pada tikus striatum.[12] Aktivasi meningkatkan pelepasan GABA pada nukleus anterior nucleus accumbens.[13] Reseptor CCK-B memodulasi pelepasan dopamin, dan memengaruhi perkembangan toleransi terhadap opioid.[14] Aktivasi CCK-B mengurangi pelepasan dopamin yang diinduksi amfetamin, dan berkontribusi terhadap variabilitas individu sebagai respons terhadap amfetamin.[15]

Pada tikus, antagonisme CCK-B mencegah reaktivasi yang diinduksi stres dari preferensi tempat yang dikondisikan oleh kokain, dan mencegah pemeliharaan jangka panjang dan pemulihan CPP yang diinduksi morfin.[16] Blokade CCK-B mempotensiasi luapan dopamin yang diinduksi kokain dalam striatum tikus.[12] CCK-B dapat berperan sebagai modulasi dalam penyakit Parkinson. Blokade CCK-B pada monyet tupai yang kekurangan dopamin menginduksi peningkatan respons lokomotor yang signifikan terhadap L-DOPA.[17] Satu penelitian menunjukkan bahwa halusinasi visual pada penyakit Parkinson dikaitkan dengan polimorfisme kolesistokin −45C> T, dan hubungan ini masih diamati dengan adanya genotipe TC/CC reseptor kolesistokinin-A, yang mengindikasikan kemungkinan interaksi kedua gen dalam halusinogenesis visual pada penyakit Parkinson.[18]

Efek pada saluran pencernaan

Reseptor kolesistokinin B distimulasi oleh CCK dan gastrin di lambung selama pencernaan.

Ligan selektif

Reseptor kolesistokinin B merespons sejumlah ligan.

Agonis

• Kolesistokinin
• CCK-4
• Gastrin
• Progastrin[19]
• BBL-454

Antagonis

• Proglumide
• CI-988
• CI-1015
• L-365.260
• L-369.293
• YF476
• YM-022
• RP-69758
• LY-225.910
• LY-288.513
• PD-135.158
• PD-145.942

Agonis terbalik

• L-740.093

Bacaan lebih lanjut

• Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E (Mar 1994). "Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors". Annals of the New York Academy of Sciences. 713: 283–97. doi:10.1111/j.1749-6632.1994.tb44076.x. PMID 8185170. 
• Lee YM, Beinborn M, McBride EW, Lu M, Kolakowski LF, Kopin AS (Apr 1993). "The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization". The Journal of Biological Chemistry. 268 (11): 8164–9. PMID 7681836. 
• Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T (Oct 1994). "Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene". Cell Growth & Differentiation. 5 (10): 1127–35. PMID 7848914. 
• Miyake A (Mar 1995). "A truncated isoform of human CCK-B/gastrin receptor generated by alternative usage of a novel exon". Biochemical and Biophysical Research Communications. 208 (1): 230–7. doi:10.1006/bbrc.1995.1328. PMID 7887934. 
• Maruyama K, Sugano S (Jan 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, Ito M, Chihara K (1993). "Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 65 (3): 184–5. doi:10.1159/000133628. PMID 8222757. 
• de Weerth A, Pisegna JR, Huppi K, Wank SA (Jul 1993). "Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor". Biochemical and Biophysical Research Communications. 194 (2): 811–8. doi:10.1006/bbrc.1993.1894. PMID 8343165. 
• Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K (Aug 1993). "Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin". The Journal of Biological Chemistry. 268 (24): 18300–5. PMID 8349705. 
• Song I, Brown DR, Wiltshire RN, Gantz I, Trent JM, Yamada T (Oct 1993). "The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs". Proceedings of the National Academy of Sciences of the United States of America. 90 (19): 9085–9. doi:10.1073/pnas.90.19.9085. PMC 47506 . PMID 8415658. 
• Beinborn M, Lee YM, McBride EW, Quinn SM, Kopin AS (Mar 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 (Jun 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". The Journal of Biological Chemistry. 271 (25): 14698–706. doi:10.1074/jbc.271.25.14698. PMID 8663021. 
• Tarasova NI, Wank SA, Hudson EA, Romanov VI, Czerwinski G, Resau JH, Michejda CJ (Feb 1997). "Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor". Cell and Tissue Research. 287 (2): 325–33. doi:10.1007/s004410050757. PMID 8995203. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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 (Aug 1998). "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 Research. 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". Receptors & Channels. 6 (3): 165–77. PMID 10100325. 
• Daulhac L, Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C (Jul 1999). "Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors". The Journal of Biological Chemistry. 274 (29): 20657–63. doi:10.1074/jbc.274.29.20657. PMID 10400698. 
• Silvente-Poirot S, Escrieut C, Galès C, Fehrentz JA, Escherich A, Wank SA, Martinez J, Moroder L, Maigret B, Bouisson M, Vaysse N, Fourmy D (Aug 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". The Journal of Biological Chemistry. 274 (33): 23191–7. doi:10.1074/jbc.274.33.23191. PMID 10438490. 
• Kulaksiz H, Arnold R, Göke B, Maronde E, Meyer M, Fahrenholz F, Forssmann WG, Eissele R (Feb 2000). "Expression and cell-specific localization of the cholecystokinin B/gastrin receptor in the human stomach". Cell and Tissue Research. 299 (2): 289–98. doi:10.1007/s004410050027. PMID 10741470. 

Referensi

1. GRCh38: Ensembl release 89: ENSG00000110148 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030898 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. 
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. 
5. "CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology". Progress in Neurobiology. 58 (4): 349–79. Jul 1999. doi:10.1016/S0301-0082(98)00090-2. PMID 10368033. 
6. "Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization". Biochemical and Biophysical Research Communications. 189 (1): 296–303. Nov 1992. doi:10.1016/0006-291X(92)91557-7. PMID 1280419. 
7. "Distinct molecular mechanisms for agonist peptide binding to types A and B cholecystokinin receptors demonstrated using fluorescence spectroscopy". The Journal of Biological Chemistry. 280 (2): 1044–50. Jan 2005. doi:10.1074/jbc.M409480200. PMID 15520004. 
8. "In vitro and in vivo evaluation of 111In-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging". Journal of Nuclear Medicine. 45 (3): 485–94. Mar 2004. PMID 15001692. 
9. "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". Molecular Pharmacology. 63 (5): 973–82. May 2003. doi:10.1124/mol.63.5.973. PMID 12695525. 
10. "Entrez Gene: CCKBR cholecystokinin B receptor". 
11. "Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin". Brain Research. 483 (2): 321–6. Apr 1989. doi:10.1016/0006-8993(89)90176-5. PMID 2706523. 
12. "Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum". Life Sciences. 73 (6): 727–39. Jun 2003. doi:10.1016/S0024-3205(03)00393-X. PMID 12801594. 
13. "Cholecystokinin (CCK) increases GABA release in the rat anterior nucleus accumbens via CCK(B) receptors located on glutamatergic interneurons". Naunyn-Schmiedeberg's Archives of Pharmacology. 361 (1): 33–8. Jan 2000. doi:10.1007/s002109900161. PMID 10651144. 
14. "The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat". European Journal of Pharmacology. 176 (1): 35–44. Jan 1990. doi:10.1016/0014-2999(90)90129-T. PMID 2311658. 
15. "Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion". Pharmacology Biochemistry and Behavior. 48 (4): 1019–24. Aug 1994. doi:10.1016/0091-3057(94)90214-3. PMID 7972279. 
16. "Different role of cholecystokinin (CCK)-A and CCK-B receptors in relapse to morphine dependence in rats". Behavioural Brain Research. 120 (1): 105–10. Apr 2001. doi:10.1016/S0166-4328(00)00361-2. PMID 11173090. 
17. "Modulatory role for CCK-B antagonists in Parkinson's disease". Clinical Neuropharmacology. 13 (4): 339–47. Aug 1990. doi:10.1097/00002826-199008000-00009. PMID 1976438. 
18. "Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson's disease". Pharmacogenetics. 13 (6): 365–9. Jun 2003. doi:10.1097/00008571-200306000-00008. PMID 12777967. 
19. Jin, Guangchun; Westphalen, C. Benedikt; Hayakawa, Yoku; Worthley, Daniel L.; Asfaha, Samuel; Yang, Xiangdong; Chen, Xiaowei; Si, Yiling; Wang, Hongshan (2013-10). "Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2". Gastroenterology. 145 (4): 820–830.e10. doi:10.1053/j.gastro.2013.07.034. ISSN 1528-0012. PMC 3829714 . PMID 23891976.  Periksa nilai tanggal di: |date= (bantuan)Pemeliharaan CS1: Format PMC (link)