Peptida pelepas gastrin (dalam bahasa Inggris : Gastrin-releasing peptide, GRP) merupakan suatu neuropeptida dan molekul regulator yang dikodekan pada manusia oleh gen GRP. GRP terlibat dalam berbagai proses fisiologis dan patofisiologis. Fungsi paling menonjol dari GRP adalah merangsang pelepasan gastrin dari sel G pada lambung. GRP mengkode sejumlah peptida mirip bombesin.[1][2][3][4] Preproprotein GRP yang terdiri dari 148 asam amino, setelah mengalami pemotongan peptida sinyal, diproses lebih lanjut untuk menghasilkan peptida gastrin-releasing sepanjang 27 asam amino atau neuromedin C sepanjang 10 asam amino.[5] Peptida-peptida kecil ini mengatur berbagai fungsi pada sistem gastrointestinal dan sistem saraf pusat, termasuk pelepasan hormon gastrointestinal, kontraksi sel otot polos, serta proliferasi sel epitel.[1]
Gene
Gen GRP terletak pada kromosom 18q21. PreproGRP (bentuk GRP yang belum diproses) dikodekan dalam tiga ekson yang dipisahkan oleh dua intron.[4] Penyambungan alternatif menghasilkan beberapa varian transkrip yang mengkode berbagai isoform.[1]
Sintesis
PreproGRP mengalami pemotongan oleh peptidase sinyal untuk menghasilkan pro-gastrin-releasing-peptide (proGRP), yang selanjutnya diproses melalui pemotongan proteolitik menjadi peptida GRP yang lebih kecil. Peptida-peptida kecil ini dilepaskan oleh serabut pasca-ganglion dari saraf vagus, yang menginervasi sel G di lambung dan merangsang sel tersebut untuk melepaskan gastrin. GRP berperan dalam mengatur berbagai fungsi sistem gastrointestinal dan sistem saraf pusat, termasuk pelepasan hormon gastrointestinal, kontraksi sel otot polos, serta proliferasi sel epitel.[6]
Fungsi
Peptida pelepas gastrin merupakan peptida regulator yang memicu pelepasan gastrin serta mengatur sekresi asam lambung dan fungsi motorik enterik.[6] Serabut pasca-ganglion dari saraf vagus yang menginervasi neuron bombesin/GRP di lambung melepaskan GRP, yang kemudian merangsang sel G untuk melepaskan gastrin. GRP juga berperan dalam sistem sirkadian, berfungsi dalam penyaluran sinyal cahaya ke osilator sirkadian utama di inti suprachiasmatic pada hipotalamus. GRP memediasi beberapa aspek respons stres, yang menjelaskan mengapa atropin tidak memblokir efek vagal pada pelepasan gastrin.[7]
Signifikansi Klinis
GRP dan neuromedin C diperkirakan berperan dalam patologi kanker manusia, termasuk kanker paru-paru, kolon, lambung, pankreas, payudara, dan prostat.[1]
Referensi
- 1 2 3 4 "Entrez Gene: GRP gastrin-releasing peptide".
- ↑ Spindel ER, Chin WW, Price J, Rees LH, Besser GM, Habener JF (September 1984). "Cloning and characterization of cDNAs encoding human gastrin-releasing peptide". Proceedings of the National Academy of Sciences of the United States of America. 81 (18): 5699–5703. Bibcode:1984PNAS...81.5699S. doi:10.1073/pnas.81.18.5699. PMC 391778. PMID 6207529.
- ↑ Spindel ER, Zilberberg MD, Habener JF, Chin WW (January 1986). "Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides". Proceedings of the National Academy of Sciences of the United States of America. 83 (1): 19–23. Bibcode:1986PNAS...83...19S. doi:10.1073/pnas.83.1.19. PMC 322782. PMID 3001723.
- 1 2 Lebacq-Verheyden AM, Bertness V, Kirsch I, Hollis GF, McBride OW, Battey J (January 1987). "Human gastrin-releasing peptide gene maps to chromosome band 18q21". Somatic Cell and Molecular Genetics. 13 (1): 81–86. doi:10.1007/BF02422302. PMID 3027901.
- ↑ "Neuromedin C". pubchem.ncbi.nlm.nih.gov (dalam bahasa Inggris).
- 1 2 Merali Z, McIntosh J, Anisman H (October 1999). "Role of bombesin-related peptides in the control of food intake". Neuropeptides. 33 (5): 376–386. doi:10.1054/npep.1999.0054. PMID 10657515.
- ↑ Antle MC, Silver R (March 2005). "Orchestrating time: arrangements of the brain circadian clock". Trends in Neurosciences. 28 (3): 145–151. doi:10.1016/j.tins.2005.01.003. ISSN 0166-2236. PMID 15749168.
Bacaan lebih lanjut
- Merali Z, McIntosh J, Anisman H (Oct 1999). "Role of bombesin-related peptides in the control of food intake". Neuropeptides. 33 (5): 376–386. doi:10.1054/npep.1999.0054. PMID 10657515. S2CID 22270584.
- Baraniuk JN, Lundgren JD, Shelhamer JH, Kaliner MA (Feb 1992). "Gastrin releasing peptide (GRP) binding sites in human bronchi". Neuropeptides. 21 (2): 81–84. doi:10.1016/0143-4179(92)90518-2. PMID 1557184. S2CID 40083693.
- Spindel ER, Zilberberg MD, Habener JF, Chin WW (Jan 1986). "Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides". Proceedings of the National Academy of Sciences of the United States of America. 83 (1): 19–23. Bibcode:1986PNAS...83...19S. doi:10.1073/pnas.83.1.19. PMC 322782. PMID 3001723.
- Sausville EA, Lebacq-Verheyden AM, Spindel ER, et al. (Feb 1986). "Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs". Journal of Biological Chemistry. 261 (5): 2451–2457. doi:10.1016/S0021-9258(17)35956-2. PMID 3003116.
- Lebacq-Verheyden AM, Bertness V, Kirsch I, Hollis GF, McBride OW, Battey J (Jan 1987). "Human gastrin-releasing peptide gene maps to chromosome band 18q21". Somatic Cell and Molecular Genetics. 13 (1): 81–86. doi:10.1007/BF02422302. PMID 3027901. S2CID 28347998.
- Naylor SL, Sakaguchi AY, Spindel E, Chin WW (Jan 1987). "Human gastrin-releasing peptide gene is located on chromosome 18". Somatic Cell and Molecular Genetics. 13 (1): 87–91. doi:10.1007/BF02422303. PMID 3027902. S2CID 7514856.
- Lebacq-Verheyden AM, Kasprzyk PG, Raum MG, et al. (Aug 1988). "Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor". Molecular and Cellular Biology. 8 (8): 3129–3135. doi:10.1128/MCB.8.8.3129. PMC 363540. PMID 3211139.
- Spindel ER, Chin WW, Price J, Rees LH, Besser GM, Habener JF (Sep 1984). "Cloning and characterization of cDNAs encoding human gastrin-releasing peptide". Proceedings of the National Academy of Sciences of the United States of America. 81 (18): 5699–5703. Bibcode:1984PNAS...81.5699S. doi:10.1073/pnas.81.18.5699. PMC 391778. PMID 6207529.
- Benya RV, Kusui T, Pradhan TK, Battey JF, Jensen RT (Jan 1995). "Expression and characterization of cloned human bombesin receptors". Molecular Pharmacology. 47 (1): 10–20. PMID 7838118.
- Moody TW, Zia F, Venugopal R, Korman LY, Goldstein AL, Fagarasan M (1994). "Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells". Peptides. 15 (2): 281–285. doi:10.1016/0196-9781(94)90013-2. PMID 8008632. S2CID 44503352.
- Frankel A, Tsao MS, Viallet J (Apr 1994). "Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells". Cancer Research. 54 (7): 1613–1616. PMID 8137267.
- Lü F, Jin T, Drucker DJ (Sep 1996). "Proglucagon gene expression is induced by gastrin-releasing peptide in a mouse enteroendocrine cell line". Endocrinology. 137 (9): 3710–3716. doi:10.1210/en.137.9.3710. PMID 8756537.
- Bertenshaw GP, Turk BE, Hubbard SJ, Matters GL, Bylander JE, Crisman JM, Cantley LC, Bond JS (Apr 2001). "Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity". Journal of Biological Chemistry. 276 (16): 13248–13255. doi:10.1074/jbc.M011414200. PMID 11278902.
- Lambeir AM, Durinx C, Proost P, Damme J, Scharpe S, Meester I (Nov 2001). "Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion" (PDF). FEBS Letters. 507 (3): 327–330. doi:10.1016/S0014-5793(01)02982-9. hdl:10067/366910151162165141. PMID 11696365. S2CID 26891876.
- Mason S, Smart D, Marshall IC, McKnight A, Skepper JN, McNulty S (Mar 2002). "Identification and characterisation of functional bombesin receptors in human astrocytes". European Journal of Pharmacology. 438 (1–2): 25–34. doi:10.1016/S0014-2999(02)01268-2. PMID 11906707.
- Carroll RE, Matkowskyj K, Saunthararajah Y, Sekosan M, Battey JF, Benya RV (May 2002). "Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract". Mechanisms of Development. 113 (2): 121–130. doi:10.1016/S0925-4773(02)00032-1. PMID 11960700. S2CID 15515339.
- Uchida K, Kojima A, Morokawa N, Tanabe O, Anzai C, Kawakami M, Eto Y, Yoshimura K (Dec 2002). "Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer". Journal of Cancer Research and Clinical Oncology. 128 (12): 633–640. doi:10.1007/s00432-002-0392-8. PMC 12164429. PMID 12474049. S2CID 23764903.
- Schneider J, Philipp M, Velcovsky HG, Morr H, Katz N (2003). "Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19-fragments (CYFRA 21-1) in patients with lung cancer in comparison to other lung diseases". Anticancer Research. 23 (2A): 885–893. PMID 12820318.
Pranala luar
- Gastrin-Releasing+Peptidedi National Library of Medicine ASJudul Subjek Medis (MeSH)
- Nosek TM. "Section 6/6ch2/s6ch2_35". Essentials of Human Physiology. Diarsipkan dari asli tanggal 2016-03-24.
