Emerging neuropeptide targets in inflammation: NPY and VIP

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 304, Issue 11, 2013, Pages

  Chandrasekharan, Bindu ^a   Nezami, Behtash Ghazi ^a   Srinivasan, Shanthi ^a,b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ATLANTA VA MEDICAL CENTER   (United States)

Author keywords

ENS; Inflammation; Neurogenic inflammation; Neuropeptides

Indexed keywords

ADRENALIN; BISPHOSPHONIC ACID DERIVATIVE; CYCLOOXYGENASE 2; I KAPPA B; INTERLEUKIN 10; INTERLEUKIN 1BETA; LENTIVIRUS VECTOR; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; NALPHA (DIPHENYLACETYL) N (4 HYDROXYBENZYL) DEXTRO ARGININAMIDE; NEUROPEPTIDE Y RECEPTOR AGONIST; NEUROPEPTIDE Y1 RECEPTOR; NEUROPEPTIDE Y2 RECEPTOR; NORADRENALIN; OLIGONUCLEOTIDE; PROTEIN KINASE C; SMALL INTERFERING RNA; STRESS ACTIVATED PROTEIN KINASE; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2;

ABDOMINAL OBESITY; ANTIGEN PRESENTING CELL; CELL DIFFERENTIATION; CELL JUNCTION; CELL MEMBRANE PERMEABILITY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DOWN REGULATION; HELPER CELL; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INNATE IMMUNITY; INTESTINE EPITHELIUM; INTESTINE INNERVATION; INTRACELLULAR SIGNALING; NATURAL KILLER CELL; NEUROGENIC INFLAMMATION; NEUROTRANSMITTER RELEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; STRESS; TIGHT JUNCTION; UPREGULATION;

ENS; INFLAMMATION; NEUROGENIC INFLAMMATION; NEUROPEPTIDES;

ANIMALS; CYTOKINES; ENTERIC NERVOUS SYSTEM; HUMANS; INTESTINAL MUCOSA; NEUROGENIC INFLAMMATION; NEUROPEPTIDE Y; VASOACTIVE INTESTINAL PEPTIDE;

EID: 84878636598     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00493.2012     Document Type: Review

References (91)

1. Abad C, Martinez C, Juarranz MG, Arranz A, Leceta J, Delgado M, Gomariz RP. Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease. Gastroenterology 124: 961-971, 2003.
2. Aiglstorfer I, Uffrecht A, Gessele K, Moser C, Schuster A, Merz S, Malawska B, Bernhardt G, Dove S, Buschauer A. NPY Y1 antagonists: structure-activity relationships of arginine derivatives and hybrid compounds with arpromidine-like partial structures. Regul Pept 75-76: 9-21, 1998.
3. Alonso C, Guilarte M, Vicario M, Ramos L, Rezzi S, Martinez C, Lobo B, Martin FP, Pigrau M, Gonzalez-Castro AM, Gallart M, Malagelada JR, Azpiroz F, Kochhar S, Santos J. Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability. Neurogastroenterol Motil 24: 740-746, e348-e749, 2012.
4. Anderson JM, Van Itallie CM. Tight junctions. Curr Biol 18: R941-R943, 2008.
5. Andrews JM, Holtmann G. IBD: stress causes flares of IBD-how much evidence is enough? Nat Rev Gastroenterol Hepatol 8: 13-14, 2011.
6. Arranz A, Abad C, Juarranz Y, Torroba M, Rosignoli F, Leceta J, Gomariz RP, Martinez C. Effect of VIP on TLR2 and TLR4 expression in lymph node immune cells during TNBS-induced colitis. Ann NY Acad Sci 1070: 129-134, 2006.
7. Arranz A, Juarranz Y, Leceta J, Gomariz RP, Martinez C. VIP balances innate and adaptive immune responses induced by specific stimulation of TLR2 and TLR4. Peptides 29: 948-956, 2008.
8. Baeuerle PA, Henkel T. Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141-179, 1994.
9. Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, Herzog H. Hypothalamic Y2 receptors regulate bone formation. J Clin Invest 109: 915-921, 2002.
10. Banks MR, Farthing MJ, Robberecht P, Burleigh DE. Antisecretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist in human and rat small intestine. Br J Pharmacol 144: 994-1001, 2005.
11. Bannon AW, Seda J, Carmouche M, Francis JM, Norman MH, Karbon B, McCaleb ML. Behavioral characterization of neuropeptide Y knockout mice. Brain Res 868: 79-87, 2000.
12. Bedoui S, Kawamura N, Straub RH, Pabst R, Yamamura T, von Horsten S. Relevance of neuropeptide Y for the neuroimmune crosstalk. J Neuroimmunol 134: 1-11, 2003.
13. Birch D, Knight GE, Boulos PB, Burnstock G. Analysis of innervation of human mesenteric vessels in non-inflamed and inflamed bowel-a confocal and functional study. Neurogastroenterol Motil 20: 660-670, 2008.
14. Bot I, de Jager SC, Bot M, van Heiningen SH, de Groot P, Veldhuizen RW, van Berkel TJ, von der Thusen JH, Biessen EA. The neuropeptide substance P mediates adventitial mast cell activation and induces intraplaque hemorrhage in advanced atherosclerosis. Circ Res 106: 89-92, 2010.
15. Boyer L, Sidpra D, Jevon G, Buchan AM, Jacobson K. Differential responses of VIPergic and nitrergic neurons in paediatric patients with Crohn's disease. Auton Neurosci 134: 106-114, 2007.
16. Chandrasekharan B, Bala V, Kolachala VL, Vijay-Kumar M, Jones D, Gewirtz AT, Sitaraman SV, Srinivasan S. Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis. PLoS One 3: e3304, 2008.
17. Chiu IM, von Hehn CA, Woolf CJ. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci 15: 1063-1067, 2012.
18. Christophi GP, Rong R, Holtzapple PG, Massa PT, Landas SK. Immune markers and differential signaling networks in ulcerative colitis and Crohn's disease. Inflamm Bowel Dis 18: 2342-2356, 2012.
19. Conlin VS, Wu X, Nguyen C, Dai C, Vallance BA, Buchan AM, Boyer L, Jacobson K. Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis. Am J Physiol Gastrointest Liver Physiol 297: (4) G735-G750, 2009.
20. Cooke HJ. Neurotransmitters in neuronal reflexes regulating intestinal secretion. Ann NY Acad Sci 915: 77-80, 2000.
21. Cox HM. Neuropeptide Y receptors; antisecretory control of intestinal epithelial function. Auton Neurosci 133: 76-85, 2007.
22. Cross LJ, Heaney LG, Ennis M. Further characterisation of substance P induced histamine release from human bronchoalveolar lavage mast cells. Inflamm Res 45, Suppl 1: S11-S12, 1996.
23. Czaja K, Kaleczyc J, Sienkiewicz W, Lakomy M. The influence of experimental ileitis on the neuropeptide coding of enteric neurons in the pig. Pol J Vet Sci 8: 155-163, 2005.
24. Delgado M, Ganea D. Cutting edge: is vasoactive intestinal peptide a type 2 cytokine? J Immunol 166: 2907-2912, 2001.
25. Delgado M, Gonzalez-Rey E, Ganea D. VIP/PACAP preferentially attract Th2 effectors through differential regulation of chemokine production by dendritic cells. FASEB J 18: 1453-1455, 2004.
26. Delgado M, Leceta J, Ganea D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia. J Leukoc Biol 73: 155-164, 2003.
27. Delgado M, Toscano MG, Benabdellah K, Cobo M, O'Valle F, Gonzalez-Rey E, Martin F. In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis. Arthritis Rheum 58: 1026-1037, 2008.
28. Detel D, Pugel EP, Pucar LB, Buljevic S, Varljen J. Development and resolution of colitis in mice with target deletion of dipeptidyl peptidase IV. Exp Physiol 97: 486-496, 2012.
29. Dimitrijevic M, Stanojevic S, Micic S, Vujic V, Kovacevic-Jovanovic V, Mitic K, von Horsten S, Kosec D. Neuropeptide Y (NPY) modulates oxidative burst and nitric oxide production in carrageenan-elicited granulocytes from rat air pouch. Peptides 27: 3208-3215, 2006.
30. Dimitrijevic M, Stanojevic S, Vujic V, Beck-Sickinger A, von Horsten S. Neuropeptide Y and its receptor subtypes specifically modulate rat peritoneal macrophage functions in vitro: counter regulation through Y1 and Y2/5 receptors. Regul Pept 124: 163-172, 2005.
31. Duffy LC, Zielezny MA, Riepenhoff-Talty M, Byers TE, Marshall J, Weiser MM, Graham S, Ogra PL. Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease. Dig Dis Sci 34: 1528-1535, 1989.
32. Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381: 415-421, 1996.
33. Fagerstam JP, Whiss PA, Strom M, Andersson RG. Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease. Inflamm Res 49: 466-472, 2000.
34. Fernandez-Martin A, Gonzalez-Rey E, Chorny A, Martin J, Pozo D, Ganea D, Delgado M. VIP prevents experimental multiple sclerosis by downregulating both inflammatory and autoimmune components of the disease. Ann NY Acad Sci 1070: 276-281, 2006.
35. Ferreira R, Xapelli S, Santos T, Silva AP, Cristovao A, Cortes L, Malva JO. Neuropeptide Y modulation of interleukin-1β (IL-1β)-induced nitric oxide production in microglia. J Biol Chem 285: 41921-41934, 2010.
36. Furness JB. The enteric nervous system: normal functions and enteric neuropathies. Neurogastroenterol Motil 20, Suppl 1: 32-38, 2008.
37. Gonzalez-Rey E, Chorny A, Fernandez-Martin A, Ganea D, Delgado M. Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Blood 107: 3632-3638, 2006.
38. Gonzalez-Rey E, Delgado M. Vasoactive intestinal peptide inhibits cyclooxygenase-2 expression in activated macrophages, microglia, and dendritic cells. Brain Behav Immun 22: 35-41, 2008.
39. Gonzalez-Rey E, Varela N, Chorny A, Delgado M. Therapeutical approaches of vasoactive intestinal peptide as a pleiotropic immunomodulator. Curr Pharm Des 13: 1113-1139, 2007.
40. Gozes I, Divinsky I, Pilzer I, Fridkin M, Brenneman DE, Spier AD. From vasoactive intestinal peptide (VIP) through activity-dependent neuroprotective protein (ADNP) to NAP: a view of neuroprotection and cell division. J Mol Neurosci 20: 315-322, 2003.
41. Grinninger C, Wang W, Oskoui KB, Voice JK, Goetzl EJ. A natural variant type II G protein-coupled receptor for vasoactive intestinal peptide with altered function. J Biol Chem 279: 40259-40262, 2004.
42. Hafstrom I, Ringertz B, Lundeberg T, Palmblad J. The effect of endothelin, neuropeptide Y, calcitonin gene-related peptide and substance P on neutrophil functions. Acta Physiol Scand 148: 341-346, 1993.
43. Hassani H, Lucas G, Rozell B, Ernfors P. Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling. Am J Physiol Gastrointest Liver Physiol 288: G550-G556, 2005.
44. Herrera JL, Gonzalez-Rey E, Fernandez-Montesinos R, Quintana FJ, Najmanovich R, Pozo D. Toll-like receptor stimulation differentially regulates vasoactive intestinal peptide type 2 receptor in macrophages. J Cell Mol Med 13: 3209-3217, 2009.
45. Holzer P, Reichmann F, Farzi A. Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 46: 261-274, 2012.
46. Huang MC, Miller AL, Wang W, Kong Y, Paul S, Goetzl EJ. Differential signaling of T cell generation of IL-4 by wild-type and short-deletion variant of type 2 G protein-coupled receptor for vasoactive intestinal peptide (VPAC2). J Immunol 176: 6640-6646, 2006.
47. Iijima H, Shinzaki S, Takehara T. The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care 15: 635-640, 2012.
48. Jonsson M, Norrgard O, Forsgren S. Epithelial expression of vasoactive intestinal peptide in ulcerative colitis: down-regulation in markedly inflamed colon. Dig Dis Sci 57: 303-310, 2012.
49. Kim SG, Kim JS, Kim JM, Jung HC, Song IS. Inhibition of proinflammatory cytokine expression by NF-κB (p65) antisense oligonucleotide in Helicobacter pylori-infected mice. Helicobacter 10: 559-566, 2005.
50. Kim WK, Kan Y, Ganea D, Hart RP, Gozes I, Jonakait GM. Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway. J Neurosci 20: 3622-3630, 2000.
51. Kimata H, Yoshida A, Ishioka C, Fujimoto M, Furusho K. Vasoactive intestinal peptide enhances immunoglobulin production and growth in human plasma cells via mechanisms that may involve protein kinase C. J Clin Endocrinol Metab 81: 3024-3032, 1996.
52. Klompus M, Ho W, Sharkey KA, McKay DM. Antisecretory effects of neuropeptide Y in the mouse colon are region-specific and are lost in DSS-induced colitis. Regul Pept 165: 138-145, 2010.
53. Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD, Lee EW, Burnett MS, Fricke ST, Kvetnansky R, Herzog H, Zukowska Z. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13: 803-811, 2007.
54. Leceta J, Gomariz RP, Martinez C, Abad C, Ganea D, Delgado M. Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP. Ann NY Acad Sci 921: 92-102, 2000.
55. Lu J, Zheng MH, Yan J, Chen YP, Pan JP. Effects of vasoactive intestinal peptide on phenotypic and functional maturation of dendritic cells. Int Immunopharmacol 8: 1449-1454, 2008.
56. Lukewich MK, Lomax AE. Toll-like receptor 4 activation reduces adrenal chromaffin cell excitability through a nuclear factor-βB-dependent pathway. Endocrinology 154: 351-362, 2013.
57. Margolis KG, Stevanovic K, Karamooz N, Li ZS, Ahuja A, D'Autreaux F, Saurman V, Chalazonitis A, Gershon MD. Enteric neuronal density contributes to the severity of intestinal inflammation. Gastroenterology 141: 588-598, 598. e1-e2, 2011.
58. Medina S, Del Rio M, Hernanz A, De la Fuente M. Age-related changes in the neuropeptide Y effects on murine lymphoproliferation and interleukin-2 production. Peptides 21: 1403-1409, 2000.
59. Michalski CW, Autschbach F, Selvaggi F, Shi X, Di Mola FF, Roggo A, Muller MW, Di Sebastiano P, Buchler MW, Giese T, Friess H. Increase in substance P precursor mRNA in noninflamed small-bowel sections in patients with Crohn's disease. Am J Surg 193: 476-481, 2007.
60. Neunlist M, Toumi F, Oreschkova T, Denis M, Leborgne J, Laboisse CL, Galmiche JP, Jarry A. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol 285: G1028-G1036, 2003.
61. Neurath MF, Becker C, Barbulescu K. Role of NF-kappaB in immune and inflammatory responses in the gut. Gut 43: 856-860, 1998.
62. Nguyen NK, Sartori SB, Herzog H, Tasan R, Sperk G, Singewald N. Effect of neuropeptide Y Y2 receptor deletion on emotional stress-induced neuronal activation in mice. Synapse 63: 236-246, 2009.
63. Nijhuis LE, Olivier BJ, de Jonge WJ. Neurogenic regulation of dendritic cells in the intestine. Biochem Pharmacol 80: 2002-2008, 2010.
64. Obata K, Yamanaka H, Dai Y, Tachibana T, Fukuoka T, Tokunaga A, Yoshikawa H, Noguchi K. Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. J Neurosci 23: 4117-4126, 2003.
65. Olah Z, Szabo T, Karai L, Hough C, Fields RD, Caudle RM, Blumberg PM, Iadarola MJ. Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1. J Biol Chem 276: 11021-11030, 2001.
66. Oprins JC, van der Burg C, Meijer HP, Munnik T, Groot JA. Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway. Gut 50: 314-321, 2002.
67. Pang XH, Li TK, Xie Q, He FQ, Cui de J, Chen YQ, Huang XL, Gan HT. Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide. Int J Colorect Dis 25: 1047-1053, 2010.
68. Philippe D, Dubuquoy L, Groux H, Brun V, Chuoi-Mariot MT, Gaveriaux-Ruff C, Colombel JF, Kieffer BL, Desreumaux P. Antiinflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation. J Clin Invest 111: 1329-1338, 2003.
69. Poole DP, Matsuyama H, Nguyen TV, Eriksson EM, Fowler CJ, Furness JB. Inflammation and inflammatory agents activate protein kinase C epsilon translocation and excite guinea-pig submucosal neurons. Gastroenterology 133: 1229-1239, 2007.
70. Pozo D, Delgado M. The many faces of VIP in neuroimmunology: a cytokine rather a neuropeptide? FASEB J 18: 1325-1334, 2004.
71. Quintana FJ, Zaltzman R, Fernandez-Montesinos R, Herrera JL, Gozes I, Cohen IR, Pozo D. NAP, a peptide derived from the activitydependent neuroprotective protein, modulates macrophage function. Ann NY Acad Sci 1070: 500-506, 2006.
72. Rozengurt E. Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists. J Cell Physiol 177: 507-517, 1998.
73. +) exchanger, SLC26A3 by neuropeptide Y is lipid raft dependent. Am J Physiol Gastrointest Liver Physiol 299: G1334-G1343, 2010.
74. Saurer TB, Ijames SG, Lysle DT. Neuropeptide Y Y1 receptors mediate morphine-induced reductions of natural killer cell activity. J Neuroimmunol 177: 18-26, 2006.
75. Sigalet DL, Wallace LE, Holst JJ, Martin GR, Kaji T, Tanaka H, Sharkey KA. Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2. Am J Physiol Gastrointest Liver Physiol 293: G211-G221, 2007.
76. Sousa DM, Baldock PA, Enriquez RF, Zhang L, Sainsbury A, Lamghari M, Herzog H. Neuropeptide Y Y1 receptor antagonism increases bone mass in mice. Bone 51: 8-16, 2012.
77. Straub RH, Wiest R, Strauch UG, Harle P, Scholmerich J. The role of the sympathetic nervous system in intestinal inflammation. Gut 55: 1640-1649, 2006.
78. Su L, Shen L, Clayburgh DR, Nalle SC, Sullivan EA, Meddings JB, Abraham C, Turner JR. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 136: 551-563, 2009.
79. Sun J, Ramnath RD, Bhatia M. Neuropeptide substance P upregulates chemokine and chemokine receptor expression in primary mouse neutrophils. Am J Physiol Cell Physiol 293: C696-C704, 2007.
80. Teixeira L, Sousa DM, Nunes AF, Sousa MM, Herzog H, Lamghari M. NPY revealed as a critical modulator of osteoblast function in vitro: new insights into the role of Y1 and Y2 receptors. J Cell Biochem 107: 908-916, 2009.
81. Tough IR, Forbes S, Tolhurst R, Ellis M, Herzog H, Bornstein JC, Cox HM. Endogenous peptide YY and neuropeptide Y inhibit colonic ion transport, contractility and transit differentially via Y1 and Y2 receptors. Br J Pharmacol 164: 471-484, 2011.
82. Vasina V, Barbara G, Talamonti L, Stanghellini V, Corinaldesi R, Tonini M, De Ponti F, De Giorgio R. Enteric neuroplasticity evoked by inflammation. Auton Neurosci 126-127: 264-272, 2006.
83. Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 534: 813-825, 2001.
84. Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD. Proteaseactivated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 22: 146-152, 2001.
85. Walther C, Morl K, Beck-Sickinger AG. Neuropeptide Y receptors: ligand binding and trafficking suggest novel approaches in drug development. J Pept Sci 17: 233-246, 2011.
86. Welcker K, Martin A, Kolle P, Siebeck M, Gross M. Increased intestinal permeability in patients with inflammatory bowel disease. Eur J Med Res 9: 456-460, 2004.
87. Wheway J, Herzog H, Mackay F. The Y1 receptor for NPY: a key modulator of the adaptive immune system. Peptides 28: 453-458, 2007.
88. Wheway J, MacKay CR, Newton RA, Sainsbury A, Boey D, Herzog H, Mackay F. A fundamental bimodal role for neuropeptide Y1 receptor in the immune system. J Exp Med 202: 1527-1538, 2005.
89. Wojtkiewicz J, Rowniak M, Crayton R, Barczewska M, Bladowski M, Robak A, Pidsudko Z, Majewski M. Inflammation-induced changes in the chemical coding pattern of colon-projecting neurons in the inferior mesenteric ganglia of the pig. J Mol Neurosci 46: 450-458, 2012.
90. Yukawa T, Oshitani N, Yamagami H, Watanabe K, Higuchi K, Arakawa T. Differential expression of vasoactive intestinal peptide receptor 1 expression in inflammatory bowel disease. Int J Mol Med 20: 161-167, 2007.
91. Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D, Sinha R, Virkkunen M, Mash DC, Lipsky RH, Hu XZ, Hodgkinson CA, Xu K, Buzas B, Yuan Q, Shen PH, Ferrell RE, Manuck SB, Brown SM, Hauger RL, Stohler CS, Zubieta JK, Goldman D. Genetic variation in human NPY expression affects stress response and emotion. Nature 452: 997-1001, 2008.