Urocortin
Urocortinis aproteinthat in humans is encoded by theUCNgene.Urocortin belongs to thecorticotropin-releasing factor(CRF) family of proteins which includesCRF,urotensin I,sauvagine,urocortin IIandurocortin III.Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response.[5][6][7]
Structure, localization, and interactions
[edit]Urocortin is apeptidecomposed of 40amino acids.Urocortin is composed of a singlealpha helixstructure. The humanUCNgene contains two exons, and the entirety of the coding region is contained within the second exon.[5]Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF.[8]Areas of similarity between urocortin and CRF expression include thesupraoptic nucleusand thehippocampus.[9][10]Urocortin is also expressed in areas distinct from CRF expression; these areas notably include themedian eminence,theEdinger-Westphal nucleus,and the sphenoid nucleus.[10]Additionally, Urocortin is expressed in peripheral tissues such as the heart.[11]
Urocortin is known to interact both with theCRF type 1andCRF type 2receptors.[12][13][14]Furthermore, Urocortin is thought to be the primary ligand for the CRF type 2 receptor, as it has higher binding affinity for the CRF type 2 receptor than CRF.[12]Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain.[15]
Stress response and social behavior
[edit]Urocortin is closely related to CRF, which mediates the mammalian stress response. Urocortin is consequently implicated in a number of stress responses, primarily relating to appetite and food intake. Administration of urocortin to the central nervous system of mice and rats has been shown to decrease appetite.[16]Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats.[16]These general anxiety-linked behaviors are likely induced through the CRF type 1 receptor, and the appetite behaviors are likely induced through the CRF type 2 receptor. The reduction in appetite from urocortin treatment could be a result of suppression of gastric emptying and/or hypoglycemia, which have been shown to result from urocortin treatment.[17]Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in thesupraoptic nucleus.[18]
Montane VolesandMeadow Volesare closely related species of voles which are regularly studied as a model for social and mating behavior. The distribution of urocortin-expressing neurons differs in meadow voles compared to montane voles, suggesting urocortin may also play a role in modulating social behavior in some species.[19]
Cardiovascular effects
[edit]Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally.[11]These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in thecardiac atriaand ventricles.[20]Urocortin also functions to protect cardiovascular tissue fromischemicinjury.[21]Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.
In non-mammals
[edit]Urocortin is not present in all non-mammals; the closet analogue inteleostfish is urotensin I.[22]However, in amphibian species such asXenopus laevis,urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin inXenopushas been shown to increasecAMPaccumulation and inhibit appetite[22]
References
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- ^"Entrez Gene: UCN urocortin".
- ^Furman BL (2007-01-01). "Urocortin".XPharm: The Comprehensive Pharmacology Reference.New York: Elsevier. pp. 1–2.doi:10.1016/B978-008055232-3.62835-1.ISBN978-0-08-055232-3.
- ^Smagin GN, Heinrichs SC, Dunn AJ (2001). "The role of CRH in behavioral responses to stress".Peptides.22(5): 713–24.CiteSeerX10.1.1.337.3880.doi:10.1016/S0196-9781(01)00384-9.PMID11337084.S2CID15756279.
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- ^abLatchman DS (August 2002). "Urocortin".The International Journal of Biochemistry & Cell Biology.34(8): 907–10.doi:10.1016/S1357-2725(02)00011-0.PMID12007627.
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- ^Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin".Neuropharmacology.36(10): 1439–46.doi:10.1016/S0028-3908(97)00098-1.PMID9423932.S2CID6235036.
- ^Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (May 1996)."Cloning and characterization of human urocortin".Endocrinology.137(5): 2167–70.doi:10.1210/endo.137.5.8612563.PMID8612563.
- ^Baigent SM, Lowry PJ (2000)."Urocortin is the principal ligand for the corticotrophin-releasing factor binding protein in the ovine brain with no evidence for a sauvagine-like peptide".Journal of Molecular Endocrinology.24(1): 53–63.doi:10.1677/jme.0.0240053.PMID10656997.
- ^abSkelton KH, Owens MJ, Nemeroff CB (2000). "The neurobiology of urocortin".Regulatory Peptides.93(1–3): 85–92.doi:10.1016/S0167-0115(00)00180-4.PMID11033056.S2CID34797789.
- ^Stengel A, Taché Y (2014-01-01)."CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress".Frontiers in Neuroscience.8:52.doi:10.3389/fnins.2014.00052.PMC3957495.PMID24672423.
- ^Hara Y, Ueta Y, Isse T, Kabashima N, Shibuya I, Hattori Y, Yamashita H (1997). "Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation".Neuroscience Letters.229(1): 65–8.doi:10.1016/S0304-3940(97)00419-9.PMID9224803.S2CID6006767.
- ^Lim MM, Tsivkovskaia NO, Bai Y, Young LJ, Ryabinin AE (2006-01-01)."Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain".Brain, Behavior and Evolution.68(4): 229–40.doi:10.1159/000094360.PMC1828133.PMID16816534.
- ^Kishimoto T, Pearse RV, Lin CR, Rosenfeld MG (February 1995)."A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle".Proceedings of the National Academy of Sciences of the United States of America.92(4): 1108–12.Bibcode:1995PNAS...92.1108K.doi:10.1073/pnas.92.4.1108.PMC42647.PMID7755719.
- ^Brar BK, Jonassen AK, Stephanou A, Santilli G, Railson J, Knight RA, Yellon DM, Latchman DS (March 2000)."Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway".The Journal of Biological Chemistry.275(12): 8508–14.doi:10.1074/jbc.275.12.8508.PMID10722688.
- ^abBoorse GC, Crespi EJ, Dautzenberg FM, Denver RJ (November 2005)."Urocortins of the South African clawed frog, Xenopus laevis: conservation of structure and function in tetrapod evolution".Endocrinology.146(11): 4851–60.doi:10.1210/en.2005-0497.PMID16037378.
Further reading
[edit]- Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M (March 2004)."Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ".FASEB Journal.18(3): 439–56.CiteSeerX10.1.1.325.45.doi:10.1096/fj.03-0641rev.PMID15003990.S2CID15642270.
- Huang Y, Yao XQ, Lau CW, Chan YC, Tsang SY, Chan FL (Mar 2004). "Urocortin and cardiovascular protection".Acta Pharmacol. Sin.25(3): 257–65.PMID15000874.
- Takahashi, Kazuhiro (2004)."Translational medicine in fish-derived peptides: From fish endocrinology to human physiology and diseases".Endocrine Journal.51(1): 1–17.doi:10.1507/endocrj.51.1.PMID15004403.
- Adachi T, Schamel WW, Kim KM, Watanabe T, Becker B, Nielsen PJ, Reth M (April 1996)."The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence".The EMBO Journal.15(7): 1534–41.doi:10.1002/j.1460-2075.1996.tb00497.x.PMC450061.PMID8612576.
- Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T (November 1997)."Urocortin expression in human pituitary gland and pituitary adenoma".The Journal of Clinical Endocrinology and Metabolism.82(11): 3842–50.doi:10.1210/jc.82.11.3842.hdl:10271/1571.PMID9360550.
- Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin".Neuropharmacology.36(10): 1439–46.doi:10.1016/S0028-3908(97)00098-1.PMID9423932.S2CID6235036.
- Bamberger CM, Wald M, Bamberger AM, Ergün S, Beil FU, Schulte HM (February 1998)."Human lymphocytes produce urocortin, but not corticotropin-releasing hormone".The Journal of Clinical Endocrinology and Metabolism.83(2): 708–11.doi:10.1210/jcem.83.2.4693.PMID9467598.
- Takahashi K, Totsune K, Sone M, Murakami O, Satoh F, Arihara Z, Sasano H, Iino K, Mouri T (1998). "Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain".Peptides.19(4): 643–7.doi:10.1016/S0196-9781(98)00012-6.PMID9622018.S2CID45625371.
- Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Takahashi K, Suzuki H, Tezuka F, Yoshimi T, Nagura H (January 1999). "Urocortin expression in the human central nervous system".Clinical Endocrinology.50(1): 107–14.doi:10.1046/j.1365-2265.1999.00624.x.PMID10341863.S2CID29828148.
- Watanabe F, Oki Y, Ozawa M, Masuzawa M, Iwabuchi M, Yoshimi T, Nishiguchi T, Iino K, Sasano H (1999). "Urocortin in human placenta and maternal plasma".Peptides.20(2): 205–9.doi:10.1016/S0196-9781(98)00175-2.PMID10422876.S2CID40604220.
- Slominski A, Roloff B, Curry J, Dahiya M, Szczesniewski A, Wortsman J (February 2000)."The skin produces urocortin".The Journal of Clinical Endocrinology and Metabolism.85(2): 815–23.doi:10.1210/jcem.85.2.6381.PMID10690896.
- Muramatsu Y, Fukushima K, Iino K, Totsune K, Takahashi K, Suzuki T, Hirasawa G, Takeyama J, Ito M, Nose M, Tashiro A, Hongo M, Oki Y, Nagura H, Sasano H (December 2000). "Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa".Peptides.21(12): 1799–809.doi:10.1016/S0196-9781(00)00335-1.PMID11150640.S2CID561707.
- Muramatsu Y, Sugino N, Suzuki T, Totsune K, Takahashi K, Tashiro A, Hongo M, Oki Y, Sasano H (March 2001)."Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries".The Journal of Clinical Endocrinology and Metabolism.86(3): 1362–9.doi:10.1210/jcem.86.3.7299.PMID11238533.
- Hsu SY, Hsueh AJ (May 2001). "Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor".Nature Medicine.7(5): 605–11.doi:10.1038/87936.PMID11329063.S2CID22916906.
- Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (June 2001)."Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor".Proceedings of the National Academy of Sciences of the United States of America.98(13): 7570–5.Bibcode:2001PNAS...98.7570L.doi:10.1073/pnas.121165198.PMC34709.PMID11416224.
- Kimura Y, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Darnel AD, Suzuki T, Ebina M, Nukiwa T, Sasano H (January 2002)."Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart".The Journal of Clinical Endocrinology and Metabolism.87(1): 340–6.doi:10.1210/jcem.87.1.8160.PMID11788672.
- Florio P, Arcuri F, Ciarmela P, Runci Y, Romagnoli R, Cintorino M, Di Blasio AM, Petraglia F (May 2002)."Identification of urocortin mRNA and peptide in the human endometrium".The Journal of Endocrinology.173(2): R9–14.doi:10.1677/joe.0.173R009.PMID12010647.
- Arcuri F, Cintorino M, Florio P, Floccari F, Pergola L, Romagnoli R, Petraglia F, Tosi P, Teresa Del Vecchio M (August 2002). "Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma".The Prostate.52(3): 167–72.doi:10.1002/pros.10094.PMID12111693.S2CID29785784.
- Ikeda K, Tojo K, Oki Y, Nakao K (September 2002). "Urocortin has cell-proliferative effects on cardiac non-myocytes".Life Sciences.71(16): 1929–38.doi:10.1016/S0024-3205(02)01945-8.PMID12175707.