Adrenomedullin regulates intestinal physiology and pathophysiology

Domestic Animal Endocrinology

Volumn 56, Issue , 2016, Pages S66-S83

  Martinez Herrero S ^a   Martinez A ^a  

^a CENTER FOR BIOMEDICAL RESEARCH OF LA RIOJA CIBIR   (Spain)

Author keywords

Adrenomedullin; Gut; Intestinal pathology; Intestinal physiology; Microbiota; PAMP

Indexed keywords

ADRENOMEDULLIN; ADRENOMEDULLIN RECEPTOR;

ANIMAL; GENE EXPRESSION REGULATION; INTESTINE; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ADRENOMEDULLIN; ANIMALS; GENE EXPRESSION REGULATION; INTESTINES; RECEPTORS, ADRENOMEDULLIN; SIGNAL TRANSDUCTION;

EID: 84979879791     PISSN: 07397240     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.domaniend.2016.02.004     Document Type: Review

References (211)

1. [1] Bernstein, C.N., Fried, M., Krabshuis, J.H., Cohen, H., Eliakim, R., Fedail, S., Gearry, R., Goh, K.L., Hamid, S., Khan, A.G., LeMair, A.W. Malfertheiner, Ouyang, Q., Rey, J.F., Sood, A., Steinwurz, F., Thomsen, O.O., Thomson, A., Watermeyer, G., World gastroenterology organization practice guidelines for the diagnosis and management of IBD in 2010. Inflamm Bowel Dis 16 (2010), 112–124.
2. [2] Huynh, M., Pignon, C., Gastrointestinal disease in exotic small mammals. J Exot Pet Med 22 (2013), 118–131.
3. [3] Cerquetella, M., Spaterna, A., Laus, F., Tesei, B., Rossi, G., Antonelli, E., Villanacci, V., Bassotti, G., Inflammatory bowel disease in the dog: differences and similarities with humans. World J Gastroenterol 16 (2010), 1050–1056.
4. [4] Suchodolski, J.S., Companion animals symposium: microbes and gastrointestinal health of dogs and cats. J Anim Sci 89 (2011), 1520–1530.
5. [5] Jergens, A.E., Feline idiopathic inflammatory bowel disease what we know and what remains to be unraveled. J Feline Med Surg 14 (2012), 445–458.
6. [6] Kaikkonen, R., Niinisto, K., Sykes, B., Anttila, M., Sankari, S., Raekallio, M., Diagnostic evaluation and short-term outcome as indicators of long-term prognosis in horses with findings suggestive of inflammatory bowel disease treated with corticosteroids and anthelmintics. Acta Vet Scand, 56, 2014.
7. [7] Jergens, A.E., Simpson, K.W., Inflammatory bowel disease in veterinary medicine. Front Biosci (Elite Ed) 4 (2012), 1404–1419.
8. [8] Hinson, J.P., Kapas, S., Smith, D.M., Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev 21 (2000), 138–167.
9. [9] Clementi, G., Caruso, A., Cutuli, V.M., de Bernardis, E., Prato, A., Mangano, N.G., Amico-Roxas, M., Effects of centrally of peripherally injected adrenomedullin on reserpine-induced gastric lesions. Eur J Pharmacol 360 (1998), 51–54.
10. [10] Ashizuka, S., Inatsu, H., Kita, T., Kitamura, K., The first clinical pilot study of adrenomedullin therapy in refractory ulcerative colitis: the initial six cases. Gastroenterology, 142, 2012 S353.
11. [11] Elsasser, T.H., Kahl, S., Martinez, A., Montuenga, L.M., Pio, R., Cuttitta, F., Adrenomedullin binding protein in the plasma of multiple species: characterization by radioligand blotting. Endocrinology 140 (1999), 4908–4911.
12. [12] Washimine, H., Asada, Y., Kitamura, K., Ichiki, Y., Hara, S., Yamamoto, Y., Kangawa, K., Sumiyoshi, A., Eto, T., Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue. Histochem Cell Biol 103 (1995), 251–254.
13. [13] Kanno, N., Asano, K., Teshima, K., Seki, M., Edamura, K., Tanaka, S., Cloning of prepro-adrenomedullin and MRNA expression in cats. J Vet Med Sci 72 (2010), 1345–1349.
14. [14] Hayashi, K.G., Hosoe, M., Sakumoto, R., Takahashi, T., Temporo-spatial expression of adrenomedullin and its receptors in the bovine placenta. Reprod Biol Endocrinol, 11, 2013, 62.
15. [15] Zudaire, E., Cuesta, N., Martinez, A., Cuttitta, F., Characterization of adrenomedullin in birds. Gen Comp Endocrinol 143 (2005), 10–20.
16. [16] Kanno, N., Asano, K., Teshima, K., Seki, M., Edamura, K., Uechi, M., Tanaka, S., Plasma adrenomedullin concentration in dogs with myxomatous mitral valvular disease. J Vet Med Sci 74 (2012), 739–743.
17. [17] Kanno, N., Asano, K., Teshima, K., Kutara, K., Seki, M., Edamura, K., Kano, R., Hasegawa, A., Tanaka, S., Gene expression of adrenomedullin in canine normal tissues and diseased hearts. J Vet Med Sci 71 (2009), 789–792.
18. [18] Gomez, A.P., Moreno, M.J., Iglesias, A., Coral, P.X., Hernandez, A., Endothelin 1, its endothelin type a receptor, connective tissue growth factor, platelet-derived growth factor, and adrenomedullin expression in lungs of pulmonary hypertensive and nonhypertensive chickens. Poult Sci 86 (2007), 909–916.
19. [19] Toth, B., Slovis, N.M., Constable, P.D., Taylor, S.D., Plasma adrenomedullin concentrations in critically ill neonatal foals. J Vet Intern Med 28 (2014), 1294–1300.
20. [20] Shirai, M., Shimouchi, A., Ikeda, S., Ninomiya, I., Sunagawa, K., Kangawa, K., Matsuo, H., Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats. Br J Pharmacol 121 (1997), 679–686.
21. [21] Boussery, K., Delaey, C., de Voorde, A.V., Influence of adrenomedullin on tone of isolated bovine retinal arteries. Invest Ophthalmol Vis Sci 45 (2004), 552–559.
22. [22] Takahashi, K., Totsune, K., Kikuchi, K., Murakam, O., Expression of endothelin-1 and adrenomedullin was not altered by leptin or resistin in bovine brain microvascular endothelial cells. Hypertens Res 29 (2006), 443–448.
23. [23] Dettmann, E.S., Vysniauskiene, I., Wu, R.Y., Flammer, J., Haefliger, I.O., Adrenomedullin-induced endothelium-dependent relaxation in porcine ciliary arteries. Invest Ophthalmol Vis Sci 44 (2003), 3961–3966.
24. [24] Kandler, M.A., von der Hardt, K., Mahfoud, S., Chada, M., Schoof, E., Papadopoulos, T., Rascher, W., Dotsch, J., Pilot intervention: aerosolized adrenomedullin reduces pulmonary hypertension. J Pharmacol Exp Ther 306 (2003), 1021–1026.
25. [25] Wang, G., Brumfield, B., DiCroce, M., Nelson, L., Newmyer, B.A., Flower, J., Hipskind, K., Sharma, S., Gilbert, E.R., Cline, M.A., Anorexigenic effects of central adrenomedullin are associated with hypothalamic changes in juvenile Gallus gallus. Gen Comp Endocrinol 204 (2014), 223–228.
26. [26] Rademaker, M.T., Charles, C.J., Nicholls, M.G., Richards, A.M., Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure. Clin Sci 122 (2012), 429–437.
27. [27] Kitamura, K., Kangawa, K., Kawamoto, M., Ichiki, Y., Nakamura, S., Matsuo, H., Eto, T., Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 192 (1993), 553–560.
28. [28] Beltowski, J., Jamroz, A., Adrenomedullin–what do we know 10 years since its discovery?. Pol J Pharmacol 56 (2004), 5–27.
29. [29] Takei, Y., Inoue, K., Ogoshi, M., Kawahara, T., Bannai, H., Miyano, S., Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator. FEBS Lett 556 (2004), 53–58.
30. [30] Roh, J., Chang, C.L., Bhalla, A., Klein, C., Hsu, S.Y., Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes. J Biol Chem 279 (2004), 7264–7274.
31. [31] Lopez, J., Martinez, A., Cell and molecular biology of the multifunctional peptide, adrenomedullin. Int Rev Cytol 221 (2002), 1–92.
32. [32] Perez-Castells, J., Martin-Santamaria, S., Nieto, L., Ramos, A., Martinez, A., de Pascual-Teresa, B., Jimenez-Barbero, J., Structure of micelle-bound adrenomedullin: a first step toward the analysis of its interactions with receptors and small molecules. Biopolymers 97 (2012), 45–53.
33. [33] Garayoa, M., Martínez, A., Lee, S., Pío, R., An, W.G., Neckers, L., Trepel, J., Montuenga, L.M., Ryan, H., Johnson, R., Gassmann, M., Cuttitta, F., Hypoxia-inducible factor-1 [hif-1] up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. Mol Endocrinol 14 (2000), 848–862.
34. [34] Ishimitsu, T., Hosoya, K., Tsukada, K., Minami, J., Futoh, Y., Ono, H., Ohrui, M., Hino, J., Kangawa, K., Matsuoka, H., Microsatellite DNA polymorphism of human adrenomedullin gene in normotensive subjects and patients with essential hypertension. Hypertension 38 (2001), 9–12.
35. [35] Ong, K.L., Tso, A.W., Leung, R.Y., Cherny, S.S., Sham, P.C., Lam, T.H., Cheung, B.M., Lam, K.S., A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese. Clin Chim Acta 412 (2011), 353–357.
36. [36] Glubb, D.M., McHugh, P.C., Deng, X., Joyce, P.R., Kennedy, M.A., Association of a functional polymorphism in the adrenomedullin gene (adm) with response to paroxetine. Pharmacogenomics J 10 (2010), 126–133.
37. [37] Cheung, B.M., Ong, K.L., Tso, A.W., Leung, R.Y., Cherny, S.S., Sham, P.C., Lam, T.H., Lam, K.S., Plasma adrenomedullin level is related to a single nucleotide polymorphism in the adrenomedullin gene. Eur J Endocrinol 165 (2011), 571–577.
38. [38] Hirose, T., Totsune, K., Mori, N., Mori, T., Morimoto, R., Metoki, H., Asayama, K., Kikuya, M., Ohkubo, T., Kohzuki, M., Takahashi, K., Imai, Y., Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure. Am J Physiol Renal Physiol 299 (2010), F128–F134.
39. [39] Wong, H.K., Ong, K.L., Leung, R.Y., Lam, T.H., Thomas, G.N., Lam, K.S., Cheung, B.M., A single nucleotide polymorphism of interleukin-6 gene is related to plasma adrenomedullin levels. Clin Endocrinol (Oxf) 79 (2013), 504–509.
40. [40] Wong, H.K., Ong, K.L., Leung, R.Y., Cheung, T.T., Xu, A., Lam, T.H., Lam, K.S., Cheung, B.M., Plasma level of adrenomedullin is influenced by a single nucleotide polymorphism in the adiponectin gene. PLoS One, 8, 2013, e70335.
41. [41] Martinez-Herrero, S., Martinez, A., Cancer protection elicited by a single nucleotide polymorphism close to the adrenomedullin gene. J Clin Endocrinol Metab 98 (2013), E807–E810.
42. [42] Pio, R., Elsassr, T.H., Martinez, A., Cuttitta, F., Identification, characterization, and physiological actions of factor H as an adrenomedullin binding protein present in human plasma. Microsc Res Tech 57 (2002), 23–27.
43. [43] Martinez, A., Oh, H.R., Unsworth, E.J., Bregonzio, C., Saavedra, J.M., Stetler-Stevenson, W.G., Cuttitta, F., Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator. Biochem J 383 (2004), 413–418.
44. [44] Poyner, D.R., Sexton, P.M., Marshall, I., Smith, D.M., Quirion, R., Born, W., Muff, R., Fischer, J.A., Foord, S.M., International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 54 (2002), 233–246.
45. [45] McLatchie, L.M., Fraser, N.J., Main, M.J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M.G., Foord, S.M., Ramps regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393 (1998), 333–339.
46. [46] Qi, T., Christopoulos, G., Bailey, R.J., Christopoulos, A., Sexton, P.M., Hay, D.L., Identification of n-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol 74 (2008), 1059–1071.
47. [47] Juaneda, C., Dumont, Y., Chabot, J.G., Fournier, A., Quirion, R., Adrenomedullin receptor binding sites in rat brain and peripheral tissues. Eur J Pharmacol 474 (2003), 165–174.
48. [48] Gibbons, C., Dackor, R., Dunworth, W., Fritz-Six, K., Caron, K.M., Receptor activity-modifying proteins: ramping up adrenomedullin signaling. Mol Endocrinol 21 (2007), 783–796.
49. [49] Shimekake, Y., Nagata, K., Ohta, S., Kambayashi, Y., Teraoka, H., Kitamura, K., Eto, T., Kangawa, K., Matsuo, H., Adrenomedullin stimulates two signal transduction pathways, camp accumulation and ca2+ mobilization, in bovine aortic endothelial cells. J Biol Chem 270 (1995), 4412–4417.
50. [50] Ikeda, U., Kanbe, T., Kawahara, Y., Yokoyama, M., Shimada, K., Adrenomedullin augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes. Circulation 94 (1996), 2560–2565.
51. [51] Shimosawa, T., Matsui, H., Xing, G., Itakura, K., Ando, K., Fujita, T., Organ-protective effects of adrenomedullin. Hypertens Res 26:Suppl (2003), S109–S112.
52. [52] Looi, Y.H., Kane, K.A., McPhaden, A.R., Wainwright, C.L., Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats. Br J Pharmacol 148 (2006), 599–609.
53. [53] Sata, M., Kakoki, M., Nagata, D., Nishimatsu, H., Suzuki, E., Aoyagi, T., Sugiura, S., Kojima, H., Nagano, T., Kangawa, K., Matsuo, H., Omata, M., Nagai, R., Hirata, Y., Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. Hypertension 36 (2000), 83–88.
54. [54] Szokodi, I., Kinnunen, P., Tavi, P., Weckström, M., Tóth, M., Ruskoaho, H., Evidence for camp-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation 97 (1998), 1062–1070.
55. [55] Hippenstiel, S., Witzenrath, M., Schmeck, B., Hocke, A., Krisp, M., Krüll, M., Seybold, J., Seeger, W., Rascher, W., Schütte, H., Suttorp, N., Adrenomedullin reduces endothelial hyperpermeability. Circ Res 91 (2002), 618–625.
56. [56] Kureishi, Y., Kobayashi, S., Nishimura, J., Nakano, T., Kanaide, H., Adrenomedullin decreases both cytosolic ca2+ concentration and ca[2+]-sensitivity in pig coronary arterial smooth muscle. Biochem Biophys Res Commun 212 (1995), 572–579.
57. [57] Nishimatsu, H., Suzuki, E., Nagata, D., Moriyama, N., Satonaka, H., Walsh, K., Sata, M., Kangawa, K., Matsuo, H., Goto, A., Kitamura, T., Hirata, Y., Adrenomedullin induces endothelium-dependent vasorelaxation via the phosphatidylinositol 3-kinase/akt-dependent pathway in rat aorta. Circ Res 89 (2001), 63–70.
58. [58] Fernandez-Sauze, S., Delfino, C., Mabrouk, K., Dussert, C., Chinot, O., Martin, P.M., Grisoli, F., Ouafik, L., Boudouresque, F., Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: involvement of crlr/ramp2 and crlr/ramp3 receptors. Int J Cancer 108 (2004), 797–804.
59. [59] Okumura, H., Nagaya, N., Itoh, T., Okano, I., Hino, J., Mori, K., Tsukamoto, Y., Ishibashi-Ueda, H., Miwa, S., Tambara, K., Toyokuni, S., Yutani, C., Kangawa, K., Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/akt-dependent pathway. Circulation 109 (2004), 242–248.
60. [60] Fritz-Six, K.L., Dunworth, W.P., Li, M., Caron, K.M., Adrenomedullin signaling is necessary for murine lymphatic vascular development. J Clin Invest 118 (2008), 40–50.
61. [61] Iwasaki, H., Shichiri, M., Marumo, F., Hirata, Y., Adrenomedullin stimulates proline-rich tyrosine kinase 2 in vascular smooth muscle cells. Endocrinology 142 (2001), 564–572.
62. [62] Parameswaran, N., Nambi, P., Brooks, D.P., Spielman, W.S., Regulation of glomerular mesangial cell proliferation in culture by adrenomedullin. Eur J Pharmacol 372 (1999), 85–95.
63. [63] Shindo, T., Kurihara, Y., Nishimatsu, H., Moriyama, N., Kakoki, M., Wang, Y., Imai, Y., Ebihara, A., Kuwaki, T., Ju, K.H., Minamino, N., Kangawa, K., Ishikawa, T., Fukuda, M., Akimoto, Y., Kawakami, H., Imai, T., Morita, H., Yazaki, Y., Nagai, R., Hirata, Y., Kurihara, H., Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation 104 (2001), 1964–1971.
64. [64] Dackor, R.T., Fritz-Six, K., Dunworth, W.P., Gibbons, C.L., Smithies, O., Caron, K.M., Hydrops fetalis, cardiovascular defects, and embryonic lethality in mice lacking the calcitonin receptor-like receptor gene. Mol Cell Biol 26 (2006), 2511–2518.
65. [65] Ichikawa-Shindo, Y., Sakurai, T., Kamiyoshi, A., Kawate, H., Iinuma, N., Yoshizawa, T., Koyama, T., Fukuchi, J., Iimuro, S., Moriyama, N., Kawakami, H., Murata, T., Kangawa, K., Nagai, R., Shindo, T., The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. J Clin Invest 118 (2008), 29–39.
66. [66] Koyama, T., Ochoa-Callejero, L., Sakurai, T., Kamiyoshi, A., Ichikawa-Shindo, Y., Iinuma, N., Arai, T., Yoshizawa, T., Iesato, Y., Lei, Y., Uetake, R., Okimura, A., Yamauchi, A., Tanaka, M., Igarashi, K., Toriyama, Y., Kawate, H., Adams, R.H., Kawakami, H., Mochizuki, N., Martinez, A., Shindo, T., Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis. Circulation 127 (2013), 842–853.
67. [67] Dackor, R., Fritz-Six, K., Smithies, O., Caron, K., Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. J Biol Chem 282 (2007), 18094–18099.
68. [68] Plück, A., Conditional mutagenesis in mice: the Cre/loxP recombination system. Int J Exp Pathol 77 (1996), 269–278.
69. [69] Julian, M., Cacho, M., Garcia, M.A., Martin-Santamaria, S., de Pascual-Teresa, B., Ramos, A., Martinez, A., Cuttitta, F., Adrenomedullin: a new target for the design of small molecule modulators with promising pharmacological activities. Eur J Med Chem 40 (2005), 737–750.
70. [70] Nicholls, M.G., Hemodynamic and hormonal actions of adrenomedullin. Braz J Med Biol Res 37 (2004), 1247–1253.
71. [71] Hayakawa, H., Hirata, Y., Kakoki, M., Suzuki, Y., Nishimatsu, H., Nagata, D., Suzuki, E., Kikuchi, K., Nagano, T., Kangawa, K., Matsuo, H., Sugimoto, T., Omata, M., Role of nitric oxide-cgmp pathway in adrenomedullin-induced vasodilation in the rat. Hypertension 33 (1999), 689–693.
72. [72] Wangensteen, R., Quesada, A., Sainz, J., Duarte, J., Vargas, F., Osuna, A., Role of endothelium-derived relaxing factors in adrenomedullin-induced vasodilation in the rat kidney. Eur J Pharmacol 444 (2002), 97–102.
73. [73] Yang, B.C., Lippton, H., Gumusel, B., Hyman, A., Mehta, J.L., Adrenomedullin dilates rat pulmonary artery rings during hypoxia: role of nitric oxide and vasodilator prostaglandins. J Cardiovasc Pharmacol 28 (1996), 458–462.
74. [74] Samson, W.K., Murphy, T.C., Resch, Z.T., Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats. Am J Physiol 274 (1998), R1505–R1509.
75. [75] Martinez, A., A new family of angiogenic factors. Cancer Lett 236 (2006), 157–163.
76. [76] Garcia-Honduvilla, N., Cifuentes, A., Bellon, J.M., Bujan, J., Martinez, A., The angiogenesis promoter, proadrenomedullin n-terminal 20 peptide (PAMP), improves healing in both normoxic and ischemic wounds either alone or in combination with autologous stem/progenitor cells. Histol Histopathol 28 (2013), 115–125.
77. [77] Nishikimi, T., Adrenomedullin in the kidney-renal physiological and pathophysiological roles. Curr Med Chem 14 (2007), 1689–1699.
78. [78] Jougasaki, M., Wei, C.M., Aarhus, L.L., Heublein, D.M., Sandberg, S.M., Burnett, J.C., Renal localization and actions of adrenomedullin: a natriuretic peptide. Am J Physiol 268 (1995), F657–F663.
79. [79] Zudaire, E., Cuttitta, F., Martínez, A., Regulation of pancreatic physiology by adrenomedullin and its binding protein. Regul Pept 112 (2003), 121–130.
80. [80] Marinoni, E., Di Iorio, R., Villaccio, B., Letizia, C., Aragona, C., Schimberni, M., Cosmi, E.V., Follicular fluid adrenomedullin concentrations in spontaneous and stimulated cycles: relationship to ovarian function and endothelin-1 and nitric oxide. Regul Pept 107 (2002), 125–128.
81. [81] Garayoa, M., Bodegas, E., Cuttitta, F., Montuenga, L.M., Adrenomedullin in mammalian embryogenesis. Microsc Res Tech 57 (2002), 40–54.
82. [82] Kobayashi, K., Kubota, T., Aso, T., Hirata, Y., Imai, T., Marumo, F., Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta. Eur J Endocrinol 142 (2000), 683–687.
83. [83] Marutsuka, K., Hatakeyama, K., Sato, Y., Yamashita, A., Sumiyoshi, A., Asada, Y., Immunohistological localization and possible functions of adrenomedullin. Hypertens Res 26:Suppl (2003), S33–S40.
84. [84] Miyashita, K., Itoh, H., Arai, H., Suganami, T., Sawada, N., Fukunaga, Y., Sone, M., Yamahara, K., Yurugi-Kobayashi, T., Park, K., Oyamada, N., Taura, D., Tsujimoto, H., Chao, T.H., Tamura, N., Mukoyama, M., Nakao, K., The neuroprotective and vasculo-neuro-regenerative roles of adrenomedullin in ischemic brain and its therapeutic potential. Endocrinology 147 (2006), 1642–1653.
85. [85] Saita, M., Shimokawa, A., Kunitake, T., Kato, K., Hanamori, T., Kitamura, K., Eto, T., Kannan, H., Central actions of adrenomedullin on cardiovascular parameters and sympathetic outflow in conscious rats. Am J Physiol 274 (1998), R979–R984.
86. [86] Kis, B., Abrahám, C.S., Deli, M.A., Kobayashi, H., Niwa, M., Yamashita, H., Busija, D.W., Ueta, Y., Adrenomedullin, an autocrine mediator of blood-brain barrier function. Hypertens Res 26:Suppl (2003), S61–S70.
87. [87] Fernandez, A.P., Serrano, J., Tessarollo, L., Cuttitta, F., Martinez, A., Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions. Proc Natl Acad Sci U S A 105 (2008), 12581–12586.
88. [88] Fernandez, A.P., Serrano, J., Martinez-Murillo, R., Martinez, A., Lack of adrenomedullin in the central nervous system results in apparently paradoxical alterations on pain sensitivity. Endocrinology 151 (2010), 4908–4915.
89. [89] Wiesner, J., Vilcinskas, A., Antimicrobial peptides the ancient arm of the human immune system. Virulence 1 (2010), 440–464.
90. [90] Martínez, A., Elsasser, T.H., Muro-Cacho, C., Moody, T.W., Miller, M.J., Macri, C.J., Cuttitta, F., Expression of adrenomedullin and its receptor in normal and malignant human skin: a potential pluripotent role in the integument. Endocrinology 138 (1997), 5597–5604.
91. [91] Allaker, R.P., Kapas, S., Adrenomedullin and mucosal defence: interaction between host and microorganism. Regul Pept 112 (2003), 147–152.
92. [92] Matheson, P.J., Mays, M.P., Hurt, R.T., Harris, P.D., Garrison, R.N., Adrenomedullin is increased in the portal circulation during chronic sepsis in rats. Am J Surg 186 (2003), 519–525.
93. [93] Kishikawa, H., Nishida, J., Ichikawa, H., Kaida, S., Morishita, T., Miura, S., Hibi, T., Lipopolysaccharides stimulate adrenomedullin synthesis in intestinal epithelial cells: release kinetics and secretion polarity. Peptides 30 (2009), 906–912.
94. [94] Zhou, M., Chaudry, I.H., Wang, P., The small intestine is an important source of adrenomedullin release during polymicrobial sepsis. Am J Physiol Regul Integr Comp Physiol 281 (2001), R654–R660.
95. [95] Walsh, T.J., Martinez, A., Peter, J., Unsworth, E., Cuttitta, F., Antimicrobial activity of adrenomedullin and its gene-related peptides. Clin Infect Dis, 23, 1996 96.
96. [96] Allaker, R.P., Zihni, C., Kapas, S., An investigation into the antimicrobial effects of adrenomedullin on members of the skin, oral, respiratory tract and gut microflora. Fems Immunol Med Microbiol 23 (1999), 289–293.
97. [97] Marutsuka, K., Nawa, Y., Asada, Y., Hara, S., Kitamura, K., Eto, T., Sumiyoshi, A., Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect. Exp Physiol 86 (2001), 543–545.
98. [98] Lucyk, S., Taha, H., Yamamoto, H., Miskolzie, M., Kotovych, G., NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth. Biopolymers 81 (2006), 295–308.
99. [99] Allaker, R.P., Grosvenor, P.W., McAnerney, D.C., Sheehan, B.E., Srikanta, B.H., Pell, K., Kapas, S., Mechanisms of adrenomedullin antimicrobial action. Peptides 27 (2006), 661–666.
100. [100] Martinez, A., Bengoechea, J.A., Cuttitta, F., Molecular evolution of proadrenomedullin N-terminal 20 peptide (PAMP): evidence for gene co-option. Endocrinology 147 (2006), 3457–3461.
101. [101] Wong, H.K., Cheung, T.T., Cheung, B.M., Adrenomedullin and cardiovascular diseases. JRSM Cardiovasc Dis, 1, 2012.
102. [102] Nishikimi, T., Yoshihara, F., Mori, Y., Kangawa, K., Matsuoka, H., Cardioprotective effect of adrenomedullin in heart failure. Hypertens Res 26:Suppl (2003), S121–S127.
103. [103] Nishikimi, T., Kuwahara, K., Nakagawa, Y., Kangawa, K., Nakao, K., Adrenomedullin in cardiovascular disease: a useful biomarker, its pathological roles and therapeutic application. Curr Protein Pept Sci 14 (2013), 256–267.
104. [104] Kobayashi, K., Kitamura, K., Hirayama, N., Date, H., Kashiwagi, T., Ikushima, I., Hanada, Y., Nagatomo, Y., Takenaga, M., Ishikawa, T., Imamura, T., Koiwaya, Y., Eto, T., Increased plasma adrenomedullin in acute myocardial infarction. Am Heart J 131 (1996), 676–680.
105. [105] Nishimatsu, H., Hirata, Y., Shindo, T., Kurihara, H., Kakoki, M., Nagata, D., Hayakawa, H., Satonaka, H., Sata, M., Tojo, A., Suzuki, E., Kangawa, K., Matsuo, H., Kitamura, T., Nagai, R., Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury: studies on transgenic/knockout mice of adrenomedullin gene. Circ Res 90 (2002), 657–663.
106. [106] Nakayama, M., Takahashi, K., Murakami, O., Murakami, H., Sasano, H., Shirato, K., Shibahara, S., Adrenomedullin in monocytes and macrophages: possible involvement of macrophage-derived adrenomedullin in atherogenesis. Clin Sci (Lond) 97 (1999), 247–251.
107. [107] Kohno, M., Hanehira, T., Kano, H., Horio, T., Yokokawa, K., Ikeda, M., Minami, M., Yasunari, K., Yoshikawa, J., Plasma adrenomedullin concentrations in essential hypertension. Hypertension 27 (1996), 102–107.
108. [108] Kinoshita, H., Fujimoto, S., Kitamura, K., Matsuura, Y., Uezono, S., Hisanaga, S., Eto, T., Increased plasma levels of mature adrenomedullin in chronic glomerulonephritis. Nephron 86 (2000), 333–338.
109. [109] Chen, Y.X., Li, C.S., Prognostic value of adrenomedullin in septic patients in the ed. Am J Emerg Med 31 (2013), 1017–1021.
110. [110] Pang, L., Qi, J., Gao, Y., Jin, H., Du, J., Adrenomedullin alleviates pulmonary artery collagen accumulation in rats with pulmonary hypertension induced by high blood flow. Peptides 54 (2014), 101–107.
111. [111] Pedreño, M., Morell, M., Robledo, G., Souza-Moreira, L., Forte-Lago, I., Caro, M., O'Valle, F., Ganea, D., Gonzalez-Rey, E., Adrenomedullin protects from experimental autoimmune encephalomyelitis at multiple levels. Brain Behav Immun 37 (2014), 152–163.
112. [112] Gonzalez-Rey, E., Delgado-Maroto, V., Souza Moreira, L., Delgado, M., Neuropeptides as therapeutic approach to autoimmune diseases. Curr Pharm Des 16 (2010), 3158–3172.
113. [113] Rulle, S., Ah Kioon, M.D., Asensio, C., Mussard, J., Ea, H.K., Boissier, M.C., Liote, F., Falgarone, G., Adrenomedullin, a neuropeptide with immunoregulatory properties induces semi-mature tolerogenic dendritic cells. Immunology 136 (2012), 252–264.
114. [114] García-Unzueta, M.T., Montalbán, C., Pesquera, C., Berrazueta, J.R., Amado, J.A., Plasma adrenomedullin levels in type 1 diabetes. Relationship with clinical parameters. Diabetes Care 21 (1998), 999–1003.
115. [115] Martínez, A., Elsasser, T.H., Bhathena, S.J., Pío, R., Buchanan, T.A., Macri, C.J., Cuttitta, F., Is adrenomedullin a causal agent in some cases of type 2 diabetes?. Peptides 20 (1999), 1471–1478.
116. [116] Sah, R.P., Nagpal, S.J., Mukhopadhyay, D., Chari, S.T., New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol 10 (2013), 423–433.
117. [117] Boudouresque, F., Berthois, Y., Martin, P.M., Figarella-Branger, D., Chinot, O., Ouafik, L., [Role of adrenomedullin in glioblastomas growth]. Bull Cancer 92 (2005), 317–326.
118. [118] Miller, M.J., Martínez, A., Unsworth, E.J., Thiele, C.J., Moody, T.W., Elsasser, T., Cuttitta, F., Adrenomedullin expression in human tumor cell lines. Its potential role as an autocrine growth factor. J Biol Chem 271 (1996), 23345–23351.
119. [119] Larráyoz, I.M., Martínez-Herrero, S., García-Sanmartín, J., Ochoa-Callejero, L., Martínez, A., Adrenomedullin and tumour microenvironment. J Transl Med, 12, 2014, 339.
120. [120] Berenguer, C., Boudouresque, F., Dussert, C., Daniel, L., Muracciole, X., Grino, M., Rossi, D., Mabrouk, K., Figarella-Branger, D., Martin, P.M., Ouafik, L., Adrenomedullin, an autocrine/paracrine factor induced by androgen withdrawal, stimulates ‘neuroendocrine phenotype’ in LNCaP prostate tumor cells. Oncogene 27 (2008), 506–518.
121. [121] Martinez, A., Vos, M., Guedez, L., Kaur, G., Chen, Z., Garayoa, M., Pio, R., Moody, T., Stetler-Stevenson, W.G., Kleinman, H.K., Cuttitta, F., The effects of adrenomedullin overexpression in breast tumor cells. J Natl Cancer Inst 94 (2002), 1226–1237.
122. [122] Gröschl, M., Wendler, O., Topf, H.G., Bohlender, J., Köhler, H., Significance of salivary adrenomedullin in the maintenance of oral health: stimulation of oral cell proliferation and antibacterial properties. Regul Pept 154 (2009), 16–22.
123. [123] Tajima, A., Osamura, R.Y., Takekoshi, S., Itoh, Y., Sanno, N., Mine, T., Fujita, T., Distribution of adrenomedullin [am], proadrenomedullin n-terminal 20 peptide, and am mrna in the rat gastric mucosa by immunocytochemistry and in situ hybridization. Histochem Cell Biol 112 (1999), 139–146.
124. [124] Wang, H., Tomikawa, M., Jones, M.K., Sarfeh, I.J., Tarnawski, A.S., Ethanol injury triggers activation of adrenomedullin and its receptor genes in gastric mucosa. Dig Dis Sci 44 (1999), 1390–1400.
125. [125] Fukuda, K., Tsukada, H., Oya, M., Onomura, M., Kodama, M., Nakamura, H., Hosokawa, M., Seino, Y., Adrenomedullin promotes epithelial restitution of rat and human gastric mucosa in vitro. Peptides 20 (1999), 127–132.
126. [126] Sakata, J., Asada, Y., Shimokubo, T., Kitani, M., Inatsu, H., Kitamura, K., Kangawa, K., Matsuo, H., Sumiyoshi, A., Eto, T., Adrenomedullin in the gastrointestinal tract. Distribution and gene expression in rat and augmented gastric adrenomedullin after fasting. J Gastroenterol 33 (1998), 828–834.
127. [127] Kitani, M., Asada, Y., Sakata, J., Kitamura, K., Sumiyoshi, A., Eto, T., Cell density of adrenomedullin-immunoreactive cells in the gastric endocrine cells decreases in antral atrophic gastritis. Histopathology 34 (1999), 134–139.
128. [128] Hashimoto, H., Akimoto, M., Maeda, A., Shigemoto, M., Yamashita, K., Yokoyama, I., Changes in vasoactive substances during gastric ulcer healing. J Cardiovasc Pharmacol 36 (2000), S278–S281.
129. [129] Okumura, T., Brain or gut? Site of action of adrenomedullin to regulate gut motility. J Gastroenterol 40 (2005), 1161–1162.
130. [130] Mulder, H., Ahren, B., Karlsson, S., Sundler, F., Adrenomedullin: localization in the gastrointestinal tract and effects on insulin secretion. Regul Pept 62 (1996), 107–112.
131. [131] Fukuda, K., Tsukada, H., Onomura, M., Saito, T., Kodama, M., Nakamura, H., Taniguchi, T., Tominaga, M., Hosokawa, M., Seino, Y., Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon. Peptides 19 (1998), 1043–1047.
132. [132] Martínez, A., Weaver, C., López, J., Bhathena, S.J., Elsasser, T.H., Miller, M.J., Moody, T.W., Unsworth, E.J., Cuttitta, F., Regulation of insulin secretion and blood glucose metabolism by adrenomedullin. Endocrinology 137 (1996), 2626–2632.
133. [133] Kitani, M., Sakata, J., Asada, Y., Kitamura, K., Eto, T., Distribution and expression of adrenomedullin in human gastrointestinal tissue. Ann Clin Biochem 35:Pt 5 (1998), 643–648.
134. [134] Kravtsov, G.M., Hwang, I.S., Tang, F., The inhibitory effect of adrenomedullin in the rat ileum: cross-talk with beta3-adrenoceptor in the serotonin-induced muscle contraction. J Pharmacol Exp Ther 308 (2004), 241–248.
135. [135] Martinez, A., Unsworth, E.J., Cuttitta, F., Adrenomedullin-like immunoreactivity in the nervous system of the starfish Marthasterias glacialis. Cell Tissue Res 283 (1996), 169–172.
136. [136] Martínez, A., Hodge, D.L., Garayoa, M., Young, H.A., Cuttitta, F., Alternative splicing of the proadrenomedullin gene results in differential expression of gene products. J Mol Endocrinol 27 (2001), 31–41.
137. [137] Kiyomizu, A., Kitamura, K., Kawamoto, M., Eto, T., Distribution and molecular forms of adrenomedullin and proadrenomedullin N-terminal 20 peptide in the porcine gastrointestinal tract. J Gastroenterol 36 (2001), 18–23.
138. [138] Man, S.Y., Hwang, I.S., Li, Y.Y., O, W.S., Sheng, H.P., Tang, F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation. Neuropeptides 41 (2007), 177–187.
139. [139] García-Arumí, E., Quiles, M., López-Hellín, J., Andreu, A.L., Arbós, M.A., Schwartz, S., Effect of starvation on organ blood flow in the senescent rat. Arch Physiol Biochem 105 (1998), 337–341.
140. [140] Hussain, S., Miyazawa, R., Tomomasa, T., Kaneko, H., Takahashi, A., Watanabe, T., Arakawa, H., Morikawa, A., Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats. J Gastroenterol 40 (2005), 1123–1129.
141. [141] Martínez, A., Cuttitta, F., Teitelman, G., Expression pattern for adrenomedullin during pancreatic development in the rat reveals a common precursor with other endocrine cell types. Cell Tissue Res 293 (1998), 95–100.
142. [142] Martínez, A., Kapas, S., Miller, M.J., Ward, Y., Cuttitta, F., Coexpression of receptors for adrenomedullin, calcitonin gene-related peptide, and amylin in pancreatic beta-cells. Endocrinology 141 (2000), 406–411.
143. [143] Martínez, A., Pío, R., López, J., Cuttitta, F., Expression of the adrenomedullin binding protein, complement factor H, in the pancreas and its physiological impact on insulin secretion. J Endocrinol 170 (2001), 503–511.
144. [144] López, J., Cuesta, N., Cuttitta, F., Martínez, A., Adrenomedullin in nonmammalian vertebrate pancreas: an immunocytochemical study. Gen Comp Endocrinol 115 (1999), 309–322.
145. [145] Zudaire, E., Portal-Núñez, S., Cuttitta, F., The central role of adrenomedullin in host defense. J Leukoc Biol 80 (2006), 237–244.
146. [146] Hiroshima, Y., Bando, M., Kataoka, M., Inagaki, Y., Herzberg, M.C., Ross, K.F., Hosoi, K., Nagata, T., Kido, J., Regulation of antimicrobial peptide expression in human gingival keratinocytes by interleukin-1α. Arch Oral Biol 56 (2011), 761–767.
147. [147] McLachlan, J.L., Smith, A.J., Bujalska, I.J., Cooper, P.R., Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries. Biochim Biophys Acta 1741 (2005), 271–281.
148. [148] Rossowski, W.J., Jiang, N.Y., Coy, D.H., Adrenomedullin, amylin, calcitonin gene-related peptide and their fragments are potent inhibitors of gastric acid secretion in rats. Eur J Pharmacol 336 (1997), 51–63.
149. [149] Rossowski, W.J., Cheng, B.L., Jiang, N.Y., Coy, D.H., Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue. Br J Pharmacol 125 (1998), 1081–1087.
150. [150] Hirsch, A.B., McCuen, R.W., Arimura, A., Schubert, M.L., Adrenomedullin stimulates somatostatin and thus inhibits histamine and acid secretion in the fundus of the stomach. Regul Pept 110 (2003), 189–195.
151. [151] Clementi, G., Caruso, A., Cutuli, V.M., Mangano, N.G., Salomone, S., Lempereur, L., Prato, A., Matera, M., Amico-Roxas, M., Gastroprotective effect of adrenomedullin administered subcutaneously in the rat. Peptides 23 (2002), 1149–1153.
152. [152] Tache, Y., Brainstem neuropeptides and vagal protection of the gastric mucosal against injury: role of prostaglandins, nitric oxide and calcitonin-gene related peptide in capsaicin afferents. Curr Med Chem 19 (2012), 35–42.
153. [153] Stachniak, T.J., Krukoff, T.L., Receptor activity modifying protein 2 distribution in the rat central nervous system and regulation by changes in blood pressure. J Neuroendocrinol 15 (2003), 840–850.
154. [154] Serrano, J., Alonso, D., Fernández, A.P., Encinas, J.M., López, J.C., Castro-Blanco, S., Fernández-Vizarra, P., Richart, A., Santacana, M., Uttenthal, L.O., Bentura, M.L., Martínez-Murillo, R., Martínez, A., Cuttitta, F., Rodrigo, J., Adrenomedullin in the central nervous system. Microsc Res Tech 57 (2002), 76–90.
155. [155] Lechin, F., van der Dijs, B., Central nervous system plus autonomic nervous system disorders responsible for gastrointestinal and pancreatobiliary diseases. Dig Dis Sci 54 (2009), 458–470.
156. [156] Egerod, K.L., Engelstoft, M.S., Lund, M.L., Grunddal, K.V., Zhao, M., Barir-Jensen, D., Nygaard, E.B., Petersen, N., Holst, J.J., Schwartz, T.W., Transcriptional and functional characterization of the G protein-coupled receptor repertoire of gastric somatostatin cells. Endocrinology 156 (2015), 3909–3923.
157. [157] Salomone, S., Caruso, A., Cutuli, V.M., Mangano, N.G., Prato, A., Amico-Roxas, M., Bianchi, A., Clementi, G., Effects of adrenomedullin on the contraction of gastric arteries during reserpine-induced gastric ulcer. Peptides 24 (2003), 117–122.
158. [158] Gourcerol, G., Adelson, D.W., Million, M., Wang, L., Taché, Y., Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents. Peptides 32 (2011), 737–746.
159. [159] Martínez, V., Cuttitta, F., Taché, Y., Central action of adrenomedullin to inhibit gastric emptying in rats. Endocrinology 138 (1997), 3749–3755.
160. [160] Martinez, V., Wang, L., Taché, Y., Peripheral adrenomedullin inhibits gastric emptying through cgrp8-37 -sensitive receptors and prostaglandins pathways in rats. Peptides 27 (2006), 1376–1382.
161. [161] Ebert, E.C., The thyroid and the gut. J Clin Gastroenterol 44 (2010), 402–406.
162. [162] Jahnke, G.D., Miller, M.J., Martínez, A., Montuenga, L., Cuttitta, F., Adrenomedullin expression in the mouse mammary gland: evidence for the mature form in milk. J Mol Endocrinol 19 (1997), 279–289.
163. [163] Pio, R., Martínez, A., Elsasser, T.H., Cuttitta, F., Presence of immunoreactive adrenomedullin in human and bovine milk. Peptides 21 (2000), 1859–1863.
164. [164] Shichiri, M., Hirata, Y., Regulation of cell growth and apoptosis by adrenomedullin. Hypertens Res 26:Suppl (2003), S9–S14.
165. [165] Martínez-Herrero, S., Larráyoz, I.M., Ochoa-Callejero, L., García-Sanmartín, J., Martínez, A., Adrenomedullin as a growth and cell fate regulatory factor for adult neural stem cells. Stem Cells Int, 2012, 2012, 804717.
166. [166] Larrayoz, I.M., Ochoa-Callejero, L., Garcia-Sanmartin, J., Vicario-Abejon, C., Martinez, A., Role of adrenomedullin in the growth and differentiation of stem and progenitor cells. Int Rev Cell Mol Biol 297 (2012), 175–234.
167. [167] Takahashi, T., Interdigestive migrating motor complex -its mechanism and clinical importance. J Smooth Muscle Res 49 (2013), 99–111.
168. [168] Fernández de Arcaya, I., Lostao, M.P., Martínez, A., Berjón, A., Barber, A., Effect of adrenomedullin and proadrenomedullin N-terminal 20 peptide on sugar transport in the rat intestine. Regul Pept 129 (2005), 147–154.
169. [169] Sekine, N., Takano, K., Kimata-Hayashi, N., Kadowaki, T., Fujita, T., Adrenomedullin inhibits insulin exocytosis via pertussis toxin-sensitive G protein-coupled mechanism. Am J Physiol Endocrinol Metab 291 (2006), E9–E14.
170. [170] Tsuchida, T., Ohnishi, H., Tanaka, Y., Mine, T., Fujita, T., Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic acini. Endocrinology 140 (1999), 865–870.
171. [171] Kaneko, H., Mitsuma, T., Nagai, H., Mori, S., Iyo, T., Kusugami, K., Tache, Y., Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats. Am J Physiol 274 (1998), R1783–R1788.
172. [172] Khadzhiev, O.C., Lupal'tsov, V.I., Simonenkov, A.P., Klimenko, N.A., Tatarko, S.V., Microcirculatory disturbances in gastric mucosa during ulcer disease and effects of serotonin on their dynamics. Bull Exp Biol Med 130 (2000), 843–845.
173. [173] Leone, V., Chang, E.B., Devkota, S., Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. J Gastroenterol 48 (2013), 315–321.
174. [174] Ford, A.C., Moayyedi, P., Hanauer, S.B., Ulcerative colitis. BMJ, 346, 2013, f432.
175. [175] Tiwari, A., VanLeeuwen, J.A., McKenna, S.L.B., Keefe, G.P., Barkema, H.W., Johne's disease in Canada - Part I: clinical symptoms, pathophysiology, diagnosis, and prevalence in dairy herds. Can Vet J 47 (2006), 874–882.
176. [176] McKenna, S.L.B., Keefe, G.P., Tiwari, A., VanLeeuwen, J., Barkema, H.W., Johne's disease in Canada part II: disease impacts, risk factors, and control programs for dairy producers. Can Vet J 47 (2006), 1089–1099.
177. [177] Troughton, R.W., Frampton, C.M., Lewis, L.K., Yandle, T.G., Richards, A.M., Nicholls, M.G., Differing thresholds for modulatory effects of adrenomedullin infusion on haemodynamic and hormone responses to angiotensin II and adrenocorticotrophic hormone in healthy volunteers. Clin Sci (Lond) 101 (2001), 103–109.
178. [178] Kataoka, Y., Miyazaki, S., Yasuda, S., Nagaya, N., Noguchi, T., Yamada, N., Morii, I., Kawamura, A., Doi, K., Miyatake, K., Tomoike, H., Kangawa, K., The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction. J Cardiovasc Pharmacol 56 (2010), 413–419.
179. [179] Ashizuka, S., Ishikawa, N., Kato, J., Yamaga, J., Inatsu, H., Eto, T., Kitamura, K., Effect of adrenomedullin administration on acetic acid-induced colitis in rats. Peptides 26 (2005), 2610–2615.
180. [180] Ashizuka, S., Inagaki-Ohara, K., Kuwasako, K., Kato, J., Inatsu, H., Kitamura, K., Adrenomedullin treatment reduces intestinal inflammation and maintains epithelial barrier function in mice administered dextran sulphate sodium. Microbiol Immunol 53 (2009), 573–581.
181. [181] Talero, E., Sanchez-Fidalgo, S., de la Lastra, C.A., Illanes, M., Calvo, J.R., Motilva, V., Acute and chronic responses associated with adrenomedullin administration in experimental colitis. Peptides 29 (2008), 2001–2012.
182. [182] Talero, E., Alvarez de Sotomayor, M., Sanchez-Fidalgo, S., Motilva, V., Vascular contribution of adrenomedullin to microcirculatory improvement in experimental colitis. Eur J Pharmacol 670 (2011), 601–607.
183. [183] MacManus, C.F., Campbell, E.L., Keely, S., Burgess, A., Kominsky, D.J., Colgan, S.P., Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization. FASEB J 25 (2011), 1856–1864.
184. [184] Kaneko, A., Kono, T., Miura, N., Tsuchiya, N., Yamamoto, M., Preventive effect of TU-100 on a type-2 model of colitis in mice: possible involvement of enhancing adrenomedullin in intestinal epithelial cells. Gastroenterol Res Pract, 2013, 2013, 384057.
185. [185] Yi, Z., Fan, H., Liu, X., Tang, Q., Zuo, D., Yang, J., Adrenomedullin improves intestinal epithelial barrier function by downregulating myosin light chain phosphorylation in ulcerative colitis rats. Mol Med Rep 12 (2015), 3615–3620.
186. [186] Hayashi, Y., Narumi, K., Tsuji, S., Tsubokawa, T., Nakaya, M.A., Wakayama, T., Zuka, M., Ohshima, T., Yamagishi, M., Okada, T., Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: insights from in vitro and in vivo experimental studies. Int J Colorectal Dis 26 (2011), 1453–1462.
187. [187] Ashizuka, S., Kita, T., Inatsu, H., Kitamura, K., Adrenomedullin: a novel therapy for intractable ulcerative colitis. Inflamm Bowel Dis 19 (2013), E26–E27.
188. [188] Cudnik, M.T., Darbha, S., Jones, J., Macedo, J., Stockton, S.W., Hiestand, B.C., The diagnosis of acute mesenteric ischemia: a systematic review and meta-analysis. Acad Emerg Med 20 (2013), 1087–1100.
189. [189] Oldenburg, W.A., Lau, L.L., Rodenberg, T.J., Edmonds, H.J., Burger, C.D., Acute mesenteric ischemia: a clinical review. Arch Intern Med 164 (2004), 1054–1062.
190. [190] Zhang, F., Wu, R., Zhou, M., Blau, S.A., Wang, P., Human adrenomedullin combined with human adrenomedullin binding protein-1 is protective in gut ischemia and reperfusion injury in the rat. Regul Peptides 152 (2009), 82–87.
191. [191] Higuchi, S., Wu, R., Zhou, M., Marini, C.P., Ravikumar, T.S., Wang, P., Gut hyperpermeability after ischemia and reperfusion: attenuation with adrenomedullin and its binding protein treatment. Int J Clin Exp Pathol 1 (2008), 409–418.
192. [192] Kinross, J., Warren, O., Basson, S., Holmes, E., Silk, D., Darzi, A., Nicholson, J.K., Intestinal ischemia/reperfusion injury: defining the role of the gut microbiome. Biomark Med 3 (2009), 175–192.
193. [193] Wong, H.K., Tang, F., Cheung, T.T., Cheung, B.M., Adrenomedullin and diabetes. World J Diabetes 5 (2014), 364–371.
194. [194] Onur, O.E., Guneysel, O., Akoglu, H., Denizbasi, A., Onur, E., Adrenomedullin reduces the severity of cerulein-induced acute pancreatitis. Peptides 28 (2007), 2179–2183.
195. [195] Letizia, C., Tamburrano, G., Alo, P., Paoloni, A., Caliumi, C., Marinoni, E., di Iorio, R., d'Erasmo, E., Adrenomedullin, a new peptide, in patients with insulinoma. Eur J Endocrinol 144 (2001), 517–520.
196. [196] Keleg, S., Kayed, H., Jiang, X., Penzel, R., Giese, T., Büchler, M.W., Friess, H., Kleeff, J., Adrenomedullin is induced by hypoxia and enhances pancreatic cancer cell invasion. Int J Cancer 121 (2007), 21–32.
197. [197] Aggarwal, G., Ramachandran, V., Javeed, N., Arumugam, T., Dutta, S., Klee, G.G., Klee, E.W., Smyrk, T.C., Bamlet, W., Han, J.J., Rumie Vittar, N.B., de Andrade, M., Mukhopadhyay, D., Petersen, G.M., Fernandez-Zapico, M.E., Logsdon, C.D., Chari, S.T., Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice. Gastroenterology 143 (2012), 1510–1517.e1.
198. [198] Sagar, G., Sah, R.P., Javeed, N., Dutta, S.K., Smyrk, T.C., Lau, J.S., Giorgadze, N., Tchkonia, T., Kirkland, J.L., Chari, S.T., Mukhopadhyay, D., Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue. Gut, 2015 in press.
199. [199] Martinez-Herrero S. Caracterización de un modelo de colitis en ratones knockout inducibles para adrenomedulina., 2014, Navarra UPd [Ed.].
200. [200] Duerr, J., Gruner, M., Schubert, S.C., Haberkorn, U., Bujard, H., Mall, M.A., Use of a new-generation reverse tetracycline transactivator system for quantitative control of conditional gene expression in the murine lung. Am J Respir Cell Mol Biol 44 (2011), 244–254.
201. [201] Bäckman, C.M., Zhang, Y., Malik, N., Shan, L., Hoffer, B.J., Westphal, H., Tomac, A.C., Generalized tetracycline induced Cre recombinase expression through the ROSA26 locus of recombinant mice. J Neurosci Methods 176 (2009), 16–23.
202. [202] Martínez-Herrero S, Pérez-Matute P, Villanueva-Millán M, Oteo J, Martínez A. Changes in gut microbiota induced by lack of adrenomedullin. In: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC®], Microbiology ASf [Ed.], 2014.
203. [203] Angelakis, E., Million, M., Kankoe, S., Lagier, J.C., Armougom, F., Giorgi, R., Raoult, D., Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment. Antimicrobial Agents Chemother 58 (2014), 3342–3347.
204. [204] Larráyoz, I.M., de Luis, A., Rúa, O., Velilla, S., Cabello, J., Martínez, A., Molecular effects of doxycycline treatment on pterygium as revealed by massive transcriptome sequencing. PLoS One, 7, 2012, e39359.
205. [205] Ellis, C.L., Ma, Z.M., Mann, S.K., Li, C.S., Wu, J., Knight, T.H., Yotter, T., Hayes, T.L., Maniar, A.H., Troia-Cancio, P.V., Overman, H.A., Torok, N.J., Albanese, A., Rutledge, J.C., Miller, C.J., Pollard, R.B., Asmuth, D.M., Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr 57 (2011), 363–370.
206. [206] Dachtler, J., Hardingham, N.R., Fox, K., The role of nitric oxide synthase in cortical plasticity is sex specific. J Neurosci 32 (2012), 14994–14999.
207. [207] Wong, P.G., Armstrong, D.W., Tse, M.Y., Brander, E.P., Pang, S.C., Sex-specific differences in natriuretic peptide and nitric oxide synthase expression in ANP gene-disrupted mice. Mol Cell Biochem 374 (2013), 125–135.
208. [208] Procaccini, C., Maksimovic, M., Aitta-Aho, T., Korpi, E.R., Linden, A.M., Reversal of Novelty-induced hyperlocomotion and hippocampal c-Fos expression in GluA1 knockout male mice by the mGluR2/3 agonist LY354740. Neuroscience 250 (2013), 189–200.
209. [209] Bäckhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., Gordon, J.I., Host-bacterial mutualism in the human intestine. Science 307 (2005), 1915–1920.
210. [210] Xenoulis, P.G., Palculict, B., Allenspach, K., Steiner, J.M., Van House, A.M., Suchodolski, J.S., Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease. Fems Microbiol Ecol 66 (2008), 579–589.
211. [211] Honneffer, J.B., Minamoto, Y., Suchodolski, J.S., Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs. World J Gastroenterol 20 (2014), 16489–16497.