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VIP, PACAP, and Related Peptides: From Gene to Therapy, Volume 1070

Hubert Vaudry (Editor), Marc Laburthe (Editor)
ISBN: 978-1-57331-550-0
500 pages
August 2006, Wiley-Blackwell
VIP, PACAP, and Related Peptides: From Gene to Therapy, Volume 1070 (1573315508) cover image
This volume provides an overview on the biochemistry, physiology, and pharmacology of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and related peptides.


VIP and PACAP are undoubtedly among the most fascinating neuropeptides ever identified. They belong to the largest family of regulatory peptides, which comprises several other prominent neuroendocrine peptides including secretin (the first peptide hormone that has been identified), glucagon, and growth hormone-releasing hormone. The structural and physiological relationships of these peptides as well as their receptors provide a unique model for investigating the processes of molecular evolution leading to the diversification of multigene families.


The primary structures of VIP and PACAP have been remarkably well conserved across vertebrates, suggesting that these peptides must be involved in vital functions throughout the animal kingdom. Indeed, VIP and PACAP appear to be implicated in a large array of physiological processes such as development; growth; endocrine, cardiovascular, respiratory, reproductive and digestive functions; immune responses; and circadian rhythms. There is also clear evidence that VIP and PACAP exert both trophic and antiproliferative effects on normal and tumor cells. The beneficial influence of VIP and PACAP agonists and antagonists in various pathological states including heart failure, ischemia, asthma, impotence, and cancer has motivated the development of novel selective VIP or PACAP ligands that could potentially be used as antihypertensive, neuroprotective, bronchodilatory, vasodilatory, and/or antiproliferative drugs. The occurrence of multiple VIP/PACAP receptor subtypes and splice variants that exhibit tissue-specific expression and possess differential affinity for various ligands generates hopes for the development of new therapeutic agents that could act selectively on the desired target cells.


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1. Treatment of Renal Failure Associated with Multiple Myeloma and Other Diseases by PACAP38. (Arimura A., M. Li And V. Batuman).

2. Clues to VIP Function from Knockckout Mice. (Hamidi S.A., A.M. Szema, S. Lyubsky, K.G. Dickman, A. Degene, S.M. Mathew, J.A. Waschek and S.I. Said).

3. The Glucagon-Like Peptides: Pleiotropic Regulators of Nutrient Homeostasis. (Brubaker P.L.).

4. Secretin: a Pleiotrophic Hormone. (Chu J.Y.S., W.H. Yung and B.K.C. Chow ).

5. VIP-PACAP System in Immunity: New Insights for Multitarget Therapy. (Gomariz R.P., Y. Juarranz, C. Abad, A. Arranz, J. Leceta and C. Martinez).

6. New Insights into the Central Pacapergic System from the Phenotypes in PACAP- and PACAP Receptor-Knockout Mice. (Hashimoto H., Shintani N. and Baba A.).

7. The 3-Dimensional Structure of The N-Terminal Domain of Corticotropin Releasing Factor (CRF) Receptors. (Sushi Domains and the B1 Family of G-Protein Coupled Receptors: Perrin M.H., C.R.R. Grace, R. Riek and W.W. Vale).

8. Complexing Receptor Pharmacology: Modulation of Family B G Protein-Coupled Receptor Function by Ramps. (Sexton P.M., M. Morfis, N. Tilakaratne, D.L. Hay, M. Udawela, G. Christopoulos and A. Christopoulos).

9. New Targets for Gpcrs Coupled to Camp and Protein Kinase. (Waschek J.A., E. DiCicco-Bloom, A. Nicot and V. Lelievre).

10. Effect of VIP on TLR2 and TLR4 Expression in Lymph Node Immune Cells During TNBS-Induced Colitis. (Arranz A., C. Abad, Y. Juarranz, M. Torroba, F. Rosignoli, J. Leceta, R.P. Gomariz and C. Martinez).

11. Immunocytochemical Distribution of VIP and PACAP in the Rat Brainstem: Implications for REM Sleep Physiology. (Ahnaou A., L. Yon, M. Arluison, H. Vaudry, J. Hannibal, M. Hamon, J. Adrien and P. Bourgin).

12. Microiontophoretically Applied PACAP Blocks Excitatory Effects of Kainic Acid in Vivo. (Atlasz T., Zs. Kőszegi, N. Babai, A.Tamás, D. Reglődi, P. Kovács, I. Hernádi and R.Gábriel).

13. Search for the Optimal Monosodium Glutamate Treatment Schedule to Study the Neuroprotective Effects of PACAP in the Retina. (Babai N., T. Atlasz, A. Tamás, D. Reglődi, G. Tóth, P. Kiss and R. Gábriel).

14. Can PACAP 38 Modulate Immune and Endocrine Responses During Lipopolisaccharide (LPS) – Induced Acute Inflammation ? (Baranowska-Bik A., W. Bik, E. Wolinska-Witort, M. Chmielowska, L. Martynska and B. Baranowska).

15. The Glucagon / Miniglucagon Interplay: a New Level in the Metabolic Regulation. (Bataille D., G. Fontés, S. Costes, C. Longuet and S. Dalle).

16. Effects of VIP and VIP-DAP on Proliferation and Lipid Peroxidation in Human KB Cells. (Caraglia M., A. Dicitore, G. Giuberti, D. Cassese, M. Lepretti, M. Cartenì, A. Abbruzzese and P. Stiuso).

17. The Delayed Rectifier Channel Current IK Plays a Key Role in the Control of Programmed Cell Death by PACAP and Ethanol in Cerebellar Granule Neurons. (Castel H., D. Vaudry, Y-A. Mei, T. Lefebvre, M. Basille, L. Desrues and A. Fournier).

18. Spatial Approximation Between the C-Terminus of VIP and The N-Terminal Ectodomain of the VPAC1 Receptor. (Ceraudo E., Y-V. Tan, A. Couvineau, J-J. Lacapere and M. Laburthe).

19. PACAP and VIP Promote Initiation of Electrophysiological Activity in Differentiating Embryonic Stem Cells. (Chafai M., E. Louiset, M. Basille, M. Cazillis, D. Vaudry, W. Rostène, P. Gressens, H. Vaudry and B.J. Gonzalez).

20. Vasoactive Intestinal Peptide Generates cd4+CD25+ Regulatory T Cells In Vivo. Therapeutic Applications in Autoimmunity and Transplantation. (Chorny A., E. Gonzalez-Rey, A. Fernandez-Martin, D. Ganea and M. Delgado).

21. Endogenous Release of Secretin from the Hypothalamus. (Chu J.Y.S., W.H. Yung and B. K. C. Chow).

22. Expression of PACAP Receptors in the Frog Brain During Development. (Ciarlo M., F. Bruzzone, C. Angelini, D. Alexandre, Y. Anouar, M. Vallarino and H. Vaudry).

23. The Human VPAC1 Receptor: Identification of the N-Terminal Ectodomain as a Major VIP Binding Site by Photoaffinity Labeling and 3D Modeling: Couvineau A., Y-V. Tan, E. Ceraudo, J-J. Lacapère, S. Murail, M.J-M. Neumann and M. Laburthe.

24. VPAC2 Receptor Activation Mediates VIP Enhancement of Population Spikes in the CA1 Area of the Hippocampus: Cunha-Reis D., J.A. Ribeiro and A.M. Sebastiao.

25. Expression and GTP-Sensitivity of Peptide Histidine Isoleucine High-Affinity Binding Sites in Rat: Debaigt C., A.C. Meunier, S. Goursaud, A. Montoni, N. Pineau, A. Couvineau, M. Laburthe, J.M. Muller and T. Janet.

26. PACAP, VIP and PHI: Effects on AC-, PLC- and PLD-Driven Signaling Systems in the Primary Glial Cell Cultures: Dejda A., M. Jozwiak-Bebenista and J.Z. Nowak.

27. Vasoactive Intestinal Peptide Induces Regulatory Dendritic Cells That Prevent Acute Graft-Versus-Host Disease and Leukemia Relapse after Bone Marrow Transplantation. (Delgado M., A. Chorny, A. Fernandez-Martin, D. Ganea and E. Gonzalez-Rey.

28. VIP: The Dentritic Cell  Regulatory T Cells Axis: Delgado M., E. Gonzalez-Rey and D. Ganea).

29. VIP and PACAP Receptor Pharmacology; a Comparison of Intracellular Signalling Pathways. (Dickson L., I. Aramori, J. Sharkey and K. Finlayson).

30. Molecular Approximation Between Residue Ten of Secretin and Its Receptor Demonstrated by Photoaffinity Labeling. (Dong M. and L.J. Miller).

31. Use of Photoaffinity Labeling to Understand the Molecular Basis of Ligand Binding to the Secretin Receptor. (Dong M. and L.J. Miller).

32. PACAP and Ceramides Exert Opposite Effects on Migration, Neurite Outgrowth and Cytoskeleton Modeling. (Falluel-Morel A., D. Vaudry, N. Aubert, L. Galas, M. Bénard, M. Basille, M. Fontaine, A. Fournier, H. Vaudry and B.J. Gonzalez).

33. The Effects of PACAP and VIP on the in vitro Melatonin Secretion from the Embryonic Chicken Pineal Gland. (Faluhelyi, N., D. Reglődi And V. Csernus).

34. VIP Prevents Experimental Multiple Sclerosis by Downregulating Both Inflammatory and Autoimmune Components of the Disease. (Fernandez-Martin A., E. Gonzalez-Rey, A. Chorny, J. Martin, D. Pozo, D. Ganea and M. Delgado).

35. C-Type Natriuretic Peptide (CNP) Is Specifically Augmented by Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) In Rat Astrocytes. (Fujikawa K., T. Nagayama, K. Inoue, N. Minamino, K. Kangawa, M. Niiro and A. Miyata).

36. Aromatase Gene Expression and Regulation in the Female Rat Pituitary. (Galmiche G., S. Corvaisier and M.L. Kottler ).

37. PACAP Inhibits Oxidative Stress-Induced Activation of MAP Kinase-Dependent Apoptotic Pathway in Cultured Cardiomyocytes. (Gasz B., B. Rácz, E. Rőth, B. Borsiczky, A. Tamás, A. Boronkai, F. Gallyas, G. Tóth and D. Reglődi).

38. Modulation of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Expression in Explant Cultured Guinea Pig Cardiac Neurons. (Girard B.M., B.A. Young, T.R. Buttolph, S.L. White and R.L. Parsons).

39. VIP: an Agent with License to Kill Infective Parasites. (Gonzalez-Rey E., A. Chorny, A. Frenandez-Martin and M. Delgado).

40. PACAP Stimulates the Release of the Secretogranin II-Derived Peptide EM66 from Chromaffin Cells. (Guillemot J., D. Ait-Ali, V. Turquier, M. Montero-Hadjadje, A. Fournier, H. Vaudry, Y. Anouar and L. Yon).

41. New Non-Radioactive Technique for Vasoactive Intestinal Peptide-Receptor-Ligand Binding Studies. (Haberl I., D.S. Habringer, F. Andreae, A. Artl and W. Mosgoeller).

42. Calcium (Ca2+) Influx Through Channels Other Than Voltage-Dependent Ca2+ Channels Is Critical tothe Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)-Induced Increase in Excitability in Guinea Pig Cardiac Neurons. (Hardwick J.C., J.D. Tompkins, S.A. Locknar, L.A. Merriam, B.A. Young and R.L. Parsons).

43. Mechanisms and Modulation of Pituitary Adenylate Cyclase Activating Protein (PACAP) –Induced Ca2+ Mobilization in Human Neutrophils. (Harfi I., S. D’Hondt and E. Sariban).

44. PACAP Enhances Mouse Urinary Bladder Contractility and is Upregulated in Micturition Reflex Pathways after Cystitis. (Herrera G.M., K.M. Braas, V. May and M.A. Vizzard.).

45. Protective Role for Plasmid DNA-Mediated VIP Gene Transfer in Non-Obese Diabetic (NOD) Mice. (Herrera J.L., R. Fernández-Montesinos, E. González-Rey, M. Delgado and D. Pozo).

46. Inhibition of Self-Renewal and Induction of Neural Differentiation by PACAP in Neural Progenitor Cells. (Hirose M., H. Hashimoto, J. Iga, N. Shintani, M. Nakanishi, N. Arakawa, T. Shimada and A. Baba).

47. Presence of PACAP and VIP in Embryonic Chicken Brain. (Jozsa R., T. Hollosy, J. Nemeth, A. Tamas, A. Lubics, B. Jakab, A. Olah, I. Lengvari, A. Arimura and D. Reglodi).

48. Short-Term Fasting Differentially Alters PACAP and VIP Levels in the Brains of Rat and Chicken. (Jozsa R., J. Nemeth, A. Tamas, T. Hollosy, A. Lubics, B. Jakab, A. Olah, I. Lengvari, A. Arimura and D. Reglodi).

49. VIP Decreases TLR4 Expression Induced by LPS and TNF Treatment in Human Synovial Fibroblasts. (Juarranz Y., I. Gutiérrez-Cañas, A. Arranz, C. Martínez, C. Abad, J. Leceta, J.L. Pablos and R.P. Gomariz).

50. Effects of Systemic PACAP Treatment in Monosodium Glutamate-Induced Behavioral Changes and Retinal Degeneration. (Kiss P., A. Tamas, A. Lubics, I. Lengvari, M. Szalai, D. Hauser, Zs. Horvath, B. Racz, R. Gabriel, N. Babai, G. Toth and D. Reglodi).

51. Localization of Small Heterodimer Partner (SHP) and Secretin in Mouse Duodenal Cells. (Lam I.P.Y., L.T.O. Lee, H.S. Choi and B.K.C. Chow).

52. Differential Mechanisms for PACAP and GnRH CAMP Induction Contribute to Cross-Talk between Both Hormones in the Gonadotrope LT2 Cell Line. (Larivière S., G. Garrel, M-T. Robin, R. Counis and J. Cohen-Tannoudji).

53. Identification of Proteins Regulated by PACAP in PC12 Cells by 2D Gel Electrophoresis Coupled to Mass Spectrometry. (Lebon A., D. Seyer, P. Cosette, L. Coquet, T. Jouenne, P. Chan, J. Leprince, A. Fournier, H. Vaudry, B.J. Gonzalez and D. Vaudry).

54. Identification of Repressor Element 1 in Secretin/PACAP/VIP Genes. (Lee L.T.O., V.H.Y. Lee, P.Y. Yuen and B.K.C. Chow).

55. Retinoic Acid-Induced Human Secretin Gene Expression in Neuronal Cells Is Mediated by Cyclin-Dependent Kinase 1. (Lee L.T.O., K.C. Tan-Un and B.K.C. Chow).

56. Neuroendocrine Tumors Express PAC1 Receptors: Lieu S.N., Oh D.S., Pisegna J.R. and. P.M. Germano.

57. PAC1 Receptor: Emerging Target for Septic Shock Therapy. (Martínez C., A. Arranz, Y. Juarranz, C. Abad, M. García-Gómez, F. Rosignoli, J. Leceta and R.P. Gomariz).

58. PACAP Activates Biosynthesis and Release of Endozepines from Rat Astrocytes. (Masmoudi-Kouki O., P. Gandolfo, J. Leprince, D. Vaudry, G. Pelletier, A. Fournier, H. Vaudry and M.C. Tonon).

59. Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) on Food Intake and Locomotor Activity in the Goldfish, Carassius Auratus. (Matsuda K., K. Maruyama, T. Nakamachi, T. Miura and S. Shioda).

60. Functional Splice-Variants of the Type II G Protein-Coupled Receptor (VPAC2) for Vasoactive Intestinal Peptide in Mouse and Human Lymphocytes. (Miller A.L., D. Verma, C. Grinninger, M-C. Huang and E.J. Goetzl).

61. Comparative Anatomy of PACAP-Immunoreactive Structures in the Ventral Nerve Cord Ganglia of Lumbricid Oligochaetes. (Molnar L., E. Pollak, A. Boros, D. Reglodi, A. Tamas, I. Lengvari, A. Arimura and A. Lubics).

62. Involvement of the Adenylyl Cyclase / Protein Kinase A Signaling Pathway in the Stimulatory Effect Of PACAP On Frog Adrenocortical Cells. (Montero-Hadjadje M., C. Delarue, A. Fournier, H. Vaudry and L. Yon).

63. Breast Cancer VPAC1 Receptors. (Moody T.W. and R.T. Jensen).

64. PACAP and Type-I PACAP Receptors in Human Prostate Cancer Tissue. (Moretti C., C. Mammi, G.V. Frajese, S. Mariani, L. Gnessi, M. Arizzi, F. Wannenes and G. Frajese).

65. Lack of Trimethyltin (TMT)-Induced Elevation of Plasma Corticosterone in PACAP-Deficient Mice. (Morita Y., D. Yanagida, N. Shintani, K. Ogita, N. Nishiyama, R. Tsuchida, H. Hashimoto and A. Baba).

66. Expression of PACAP Receptor mRNAs By Neuropeptide Y Neurons in the Rat Arcuate Nucleus. (Mounien L., P. Bizet, I. Boutelet, G. Gourcerol, M. Basille, B.J. Gonzalez, H. Vaudry and S. Jégou.).

67. Developmental Dynamics of VIP Receptor in the Human Hypothalamus. (Najimi M., F. Rachidi, A. Afif and F. Chigr ).

68. Changes in PACAP Levels In The Central Nervous System After Ovariectomy And Castration. (Nemeth J., A. Tamas, R. Jozsa, J.E. Horvath, B. Jakab, I. Lengvari, A. Arimura, A. Lubics and D. Reglodi).

69. Effects of Pituitary Adenylate Cyclase-Activating Polypeptide, Vasoactive Intestinal Polypeptide, and Somatostatin on the Release of Thyrotropin from the Bullfrog Pituitary. (Okada R., K. Yamamoto, N. Chartrel, J. Leprince, A. Fournier, H. Vaudry and S. Kikuyama).

70. The Vasoactive Intestinal Peptide (VIP) Receptor Turnover in Pulmonary Arteries Indicates an Important Role of VIP in Lung Circulation. (Petkov V., T. Gentcheva, C. Schamberger, I. Haberl, A. Artl, F. Andreae and V. Mosgoeller).

71. A Splice Variant to PACAP Receptor that is Involved in Spermatogenesis is Expressed in Astrocytes. (Pilzer I. And I. Gozes).

72. Glucose Activation of the Glucagon Receptor Gene: Functional Dissimilarity with Several Other Glucose Response Elements. (Portois L., M. Virreira, M. Tastenoy and M. Svoboda).

73. NAP, a Peptide Derived From the Activity-Dependent Neuroprotective Protein (ADNP), Modulates Macrophage Function. (Quintana F.J., R. Zaltzman, R. Fernandez-Montesinos, J.L. Herrera, I. Gozes, I.R. Cohen and D. Pozo).

74. Involvement of ERK and CREB Signalling Pathways in the Protective Effect of PACAP in Monosodium Glutamate-Induced Retinal Lesion. (Rácz B., Tamás A., Kiss P., Tóth G., Gasz B., Borsiczky B., Ferencz A., Gallyas F.Jr., Rőth E. And Reglődi D.).

75. Mechanisms of VIP-Induced Neuroprotection Against Neonatal Excitotoxicity. (Rangon C.M., L. Dicou, S. Goursaud, L. Mounien, S. Jégou, T. Janet, J.M. Muller, V. Lelièvre and P. Gressens).

76. Comparative Study on the Effects Of PACAP in Young, Aging, and Castrated Males in a Rat Model of Parkinson`S Disease. (Reglodi D., A. Tamas, I. Lengvari, G. Toth, L. Szalontay and A. Lubics).

77. VIP and Tolerance Induction in Autoimmunity. (Rosignoli F., M. Torroba, Y. Juarranz, M. García-Gómez, C. Martinez, R.P. Gomariz, C. Pérez-Leirós and J. Leceta).

78. Neuroprotective Effect of PACAP Against Kainic Acid (KA)-Induced Neurotoxicity in Rat Retina. (Seki T., M. Nakatani, C. Taki, Y. Shinohara, M. Ozawa, S. Nishimura and S. Shioda).

79. PACAP Stimulates the Release of Interleukin-6 in Cultured Rat Müller Cells. (Seki T., Y. Shinohara, C. Taki, M. Nakatani, M. Ozawa, S. Nishimura, A. Takaki and S. Shioda).

80. VIP Protects TH2 Cells by Downregulating Granzyme B Expression. (Sharma V., M. Delgado and D. Ganea).

81. Serotonergic Inhibition of Intense Jumping Behavior in Mice Laking PACAP (Adgyap 1-/-). (Shintani N., H. Hashimoto, K. Tanaka, N. Kawagishi, C. Kawaguchi, M. Hatanaka, Y. Ago, T. Matsuda and A. Baba).

82. Pleiotropic Functions of PACAP in the CNS: Neuroprotection and Neurodevelopment. (Shioda S., H. Ohtaki, T. Nakamachi, K. Dohi, J. Watanabe, S. Nakajo, S. Arata, S. Kitamura, H. Okuda, F. Takenoya and Y. Kitamura).

83. The Prenatal Expression of Secretin Receptor. (Siu F.K.Y., M.H. Sham and B.K.C. Chow).

84. Cyclic AMP Formation in C6 Glioma Cells: Effect of PACAP and VIP in Early and Late Passages. (Sokolowska P. and J.A. Nowak).

85. Protective Effects of PACAP in Excitotoxic Striatal Lesion. (Tamás A., A. Lubics, I. Lengvári and D. Reglődi).

86. Characterization of the New Photoaffinity Probe (Bz2-K24)-VIP. (Tan Y-V., A. Couvineau, J-J. Lacapere and M. Laburthe).

87. PACAP Receptor (PAC1-R) Expression in Rat and Rhesus Monkey Thymus. (Tokuda N., Y. Arudchelvan, T. Sawada, Y. Adachi, T. Fukumoto, M. Yasuda, H. Sumida, S. Shioda, T. Fukuda, A. Arima and S. Kubota).

88. Characterization of the PAC1 Expressed in the Mouse Heart. (Ushiyama M., H. Sugawara, K. Inoue, K. Kangawa, K. Yamada and A. Miyata.

89. Distribution of PACAP in the Brain of Cartilaginous Fish Torpedo Marmorata: Valiante S., M. Prisco, L. Ricchiari, V. Laforgia, L. Varano and P. Andreuccetti).

90. Involvement of Protein Kinase C in the PACAP-Induced Differentiation of Neural Stem Cells into Astrocytes. (Watanabe J., F. Ohno, S. Shioda, S. Kikuyama, K. Nakaya and S. Nakajo S.).

91. Role of Two Genes Encoding PACAP in Early Brain Developement in Zebrafish. (Wu S., B.A. Adams, E.A. Fradinger and N.M. Sherwood).

92. A Role for Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in Detrusor Hyperreflexia after Spinal Cord Injury (SCI). (Zvara P., K.M. Braas, V. May and M.A. Vizzard)

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