Abstract
Vasoactive intestinal peptide (VIP) has been identified as one of major peptide transmitters in the central and peripheral nervous systems, being involved in a wide range of biological functions. The general physiologic effects of VIP include vasodilation, anti-inflammatory actions, cell proliferation, hormonal secretion, regulation of gastric motility, and smooth muscle relaxation; therefore, VIP has emerged as a promising drug candidate for the treatment of several diseases. A number of clinical applications of VIP or its derivatives have been developed; however, VIP-based drugs are not yet in clinical use, possibly because of mainly two serious problems: (1) poor metabolic stability and (2) poor penetration to the desired site of action. To overcome these shortcomings, the development of efficacious VIP analogues and several drug delivery systems has been attempted on the basis of numerous structure–activity relationships (SAR) studies and pharmacological experiments. Combination of the use of potent VIP analogues and an appropriate drug delivery system might be advantageous for the VIP-based therapy. We review in this paper SAR studies of VIP for the identification of potent therapeutic agents, describe the development of selective and/or metabolically stable VIP receptor agonists/antagonists, and discuss the potential application for clinical treatment using drug delivery systems.
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Abad C, Martinez C, Juarranz MG, Arranz A, Leceta J, Delgado M, Gomariz RP (2003) Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn’s disease. Gastroenterology 124:961–971
Abad C, Gomariz RP, Waschek JA (2006) Neuropeptide mimetics and antagonists in the treatment of inflammatory disease: focus on VIP and PACAP. Curr Top Med Chem 6:151–163
Ashok B, Rubinstein I, Tsueshita T, Onyuksel H (2004) Effects of peptide molecular mass and PEG chain length on the vasoreactivity of VIP and PACAP(1–38) in pegylated phospholipid micelles. Peptides 25:1253–1258
Basille M, Vaudry D, Coulouarn Y, Jegou S, Lihrmann I, Fournier A, Vaudry H, Gonzalez B (2000) Comparative distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites and PACAP receptor mRNAs in the rat brain during development. J Comp Neurol 425:495–509
Biancani P, Beinfeld MC, Coy DH, Hillemeier C, Walsh JH, Behar J (1988) Dysfunction of the gastrointestinal peptide in peristalsis and sphincter function. Ann N Y Acad Sci 527:545–567
Bickel U, Yoshikawa T, Landaw EM, Faull KF, Pardridge WM (1993) Pharmacologic effects in vivo in brain by vector-mediated peptide drug delivery. Proc Natl Acad Sci U S A 90:2618–2622
Blankenfeldt W, Nokihara K, Naruse S, Lessel U, Schomburg D, Wray V (1996) NMR spectroscopic evidence that helodermin, unlike other members of the secretin/VIP family of peptides, is substantially structured in water. Biochemistry 35:5955–5962
Bodanszky M, Bodanszky A (1986) Conformation of peptides of the secretin–VIP–glucagon family in solution. Peptides 7:43–48
Bodanszky M, Bodanszky A, Klausner YS, Said SI (1974) A preferred conformation in the vasoactive intestinal peptide (VIP). Molecular architecture of gastrointestinal hormones. Bioorg Chem 3:133–140
Bolin DR, Cottrell JM, O’Neill N, Garippa R, O’Donnell M (1989) N-terminal analogs of vasoactive intestinal peptide: Identification of a binding pharmacophore. In: Rivier JE, Marshall GR (eds) 11th American Peptide Symposium. ESCON Scientific, Leiden, The Netherlands, La Jolla, CA, pp 208–210
Bolin DR, Cottrell J, Michalewsky J, Garippa R, O’Neill N, Simko B, O’Donnell M (1992) Degradation of vasoactive intestinal peptide in bronchoalveolar lavage fluid. Biomed Res 13:25–30
Bolin DR, Cottrell J, Garippa R, O’Neill N, Simko B, O’Donnell M (1993) Structure-activity studies of vasoactive intestinal peptide (VIP): cyclic disulfide analogs. Int J Pept Protein Res 41:124–132
Bolin DR, Michalewsky J, Wasserman MA, O’Donnell M (1995) Design and development of a vasoactive intestinal peptide analog as a novel therapeutic for bronchial asthma. Biopolymers 37:57–66
Clore GM, Nilges M, Brunger A, Gronenborn AM (1988) Determination of the backbone conformation of secretin by restrained molecular dynamics on the basis of interproton distance data. Eur J Biochem 171:479–484
Delgado M, Martinez C, Pozo D, Calvo JR, Leceta J, Ganea D, Gomariz RP (1999a) Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-alpha and IL-6. J Immunol 162:1200–1205
Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D (1999b) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide prevent inducible nitric oxide synthase transcription in macrophages by inhibiting NF-kappa B and IFN regulatory factor 1 activation. J Immunol 162:4685–4696
Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP (2001) Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med 7:563–568
Dinsmore WW, Gingell C, Hackett G, Kell P, Savage D, Oakes R, Frentz GD (1999) Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate in a novel auto-injector system: a multicentre double-blind placebo-controlled study. BJU Int 83:274–279
Domschke S, Domschke W, Bloom SR, Mitznegg P, Mitchell SJ, Lux G, Strunz U (1978) Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut 19:1049–1053
Dufes C, Olivier JC, Gaillard F, Gaillard A, Couet W, Muller JM (2003) Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats. Int J Pharm 255:87–97
Dufes C, Gaillard F, Uchegbu IF, Schatzlein AG, Olivier JC, Muller JM (2004) Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain. Int J Pharm 285:77–85
Filipsson K, Sundler F, Hannibal J, Ahren B (1998) PACAP and PACAP receptors in insulin producing tissues: localization and effects. Regul Pept 74:167–175
Filipsson K, Kvist-Reimer M, Ahren B (2001) The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet function. Diabetes 50:1959–1969
Filizola M, Carteni-Farina M, Perez JJ (1997) Conformational study of vasoactive intestinal peptide by computational methods. J Pept Res 50:55–64
Goossens JF, Cotelle P, Chavatte P, Henichart JP (1996) NMR study of five N-terminal peptide fragments of the vasoactive intestinal peptide: crucial role of aromatic residues. Pept Res 9:322–326
Gourlet P, Vandermeers A, Vandermeers-Piret MC, De Neef P, Robberecht P (1996a) Addition of the (28–38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy. Int J Pept Protein Res 48:391–396
Gourlet P, Vilardaga JP, De Neef P, Waelbroeck M, Vandermeers A, Robberecht P (1996b) The C-terminus ends of secretin and VIP interact with the N-terminal domains of their receptors. Peptides 17:825–829
Gourlet P, De Neef P, Cnudde J, Waelbroeck M, Robberecht P (1997a) In vitro properties of a high affinity selective antagonist of the VIP1 receptor. Peptides 18:1555–1560
Gourlet P, Vandermeers A, Vertongen P, Rathe J, De Neef P, Cnudde J, Waelbroeck M, Robberecht P (1997b) Development of high affinity selective VIP1 receptor agonists. Peptides 18:1539–1545
Gourlet P, Rathe J, De Neef P, Cnudde J, Vandermeers-Piret MC, Waelbroeck M, Robberecht P (1998) Interaction of lipophilic VIP derivatives with recombinant VIP1/PACAP and VIP2/PACAP receptors. Eur J Pharmacol 354:105–111
Gozes I, Furman S (2003) VIP and drug design. Curr Pharm Des 9:483–494
Gozes I, Furman S (2004) Clinical endocrinology and metabolism. Potential clinical applications of vasoactive intestinal peptide: a selected update. Best Pract Res Clin Endocrinol Metab 18:623–640
Gozes I, Meltzer E, Rubinrout S, Brenneman DE, Fridkin M (1989) Vasoactive intestinal peptide potentiates sexual behavior: inhibition by novel antagonist. Endocrinology 125:2945–2949
Gozes I, Perl O, Giladi E, Davidson A, Ashur-Fabian O, Rubinraut S, Fridkin M (1999) Mapping the active site in vasoactive intestinal peptide to a core of four amino acids: neuroprotective drug design. Proc Natl Acad Sci U S A 96:4143–4148
Granoth R, Fridkin M, Gozes I (2000) VIP and the potent analog, stearyl-Nle(17)-VIP, induce proliferation of keratinocytes. FEBS Lett 475:78–83
Groneberg DA, Rabe KF, Fischer A (2006) Novel concepts of neuropeptide-based drug therapy: vasoactive intestinal polypeptide and its receptors. Eur J Pharmacol 533:182–194
Haghjoo K, Cash PW, Farid RS, Komisaruk BR, Jordan F, Pochapsky SS (1996) Solution structure of vasoactive intestinal polypeptide (11–28)-NH2, a fragment with analgesic properties. Pept Res 9:327–331
Hashimoto H, Ishihara T, Shigemoto R, Mori K, Nagata S (1993) Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide. Neuron 11:333–342
Hassan M, Refai E, Andersson M, Schnell PO, Jacobsson H (1994) In vivo dynamical distribution of 131I-VIP in the rat studied by gamma-camera. Nucl Med Biol 21:865–872
Hoshino M, Yanaihara C, Hong YM, Kishida S, Katsumaru Y, Vandermeers A, Vandermeers-Piret MC, Robberecht P, Christophe J, Yanaihara N (1984) Primary structure of helodermin, a VIP-secretin-like peptide isolated from Gila monster venom. FEBS Lett 178:233–239
Igarashi H, Ito T, Hou W, Mantey SA, Pradhan TK, Ulrich CD 2nd, Hocart SJ, Coy DH, Jensen RT (2002) Elucidation of vasoactive intestinal peptide pharmacophore for VPAC(1) receptors in human, rat, and guinea pig. J Pharmacol Exp Ther 301:37–50
Igarashi H, Ito T, Mantey SA, Pradhan TK, Hou W, Coy DH, Jensen RT (2005) Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors. J Pharmacol Exp Ther 315:370–381
Inooka H, Ohtaki T, Kitahara O, Ikegami T, Endo S, Kitada C, Ogi K, Onda H, Fujino M, Shirakawa M (2001) Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat Struct Biol 8:161–165
Ito O, Tachibana S (1991) Vasoactive intestinal polypeptide precursors have highly potent bronchodilatory activity. Peptides 12:131–137
Ito T, Igarashi H, Pradhan TK, Hou W, Mantey SA, Taylor JE, Murphy WA, Coy DH, Jensen RT (2001) GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. Peptides 22:1139–1151
Jorpes JE (1968) The isolation and chemistry of secretin and cholecystokinin. Gastroenterology 55:157–164
Kashimoto K, Nagano Y, Suitani Y, Hamanaka K, Mizumoto T, Tomizaki K, Takahata H, Nagamoto A, Ohata A, Yoshihara S, Ichimura T (1996a) Structure–activity relationship studies of PACAP-27 and VIP analogues. Ann N Y Acad Sci 805:505–510
Kashimoto K, Nagano Y, Suitani Y, Hamanaka K, Takahata H, Ohata A, Urauchi E, Watanabe S (1996b) The interaction studies of VIP and VIP analogue with glycosaminoglycan. In: Japanese Peptide Symposium, Tsukuba, Japan, pp 249–252
Kato H, Ito A, Kawanokuchi J, Jin S, Mizuno T, Ojika K, Ueda R, Suzumura A (2004) Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells. Mult Scler 10:651–659
Kobayashi S, Takeshima K, Park CB, Kim SC, Matsuzaki K (2000) Interactions of the novel antimicrobial peptide buforin 2 with lipid bilayers: proline as a translocation promoting factor. Biochemistry 39:8648–8654
Laburthe M, Couvineau A, Gaudin P, Maoret JJ, Rouyer-Fessard C, Nicole P (1996) Receptors for VIP, PACAP, secretin, GRF, glucagon, GLP-1, and other members of their new family of G protein-linked receptors: structure–function relationship with special reference to the human VIP-1 receptor. Ann N Y Acad Sci 805:94–109
Lilly CM, Drazen JM, Shore SA (1993) Peptidase modulation of airway effects of neuropeptides. Proc Soc Exp Biol Med 203:388–404
Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567–574
Miyata A, Jiang L, Dahl RD, Kitada C, Kubo K, Fujino M, Minamino N, Arimura A (1990) Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun 170:643–648
Mojsov S, Weir GC, Habener JF (1987) Insulinotropin: glucagon-like peptide I (7–37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 79:616–619
Moreno D, Gourlet P, De Neef P, Cnudde J, Waelbroeck M, Robberecht P (2000) Development of selective agonists and antagonists for the human vasoactive intestinal polypeptide VPAC(2) receptor. Peptides 21:1543–1549
Morice A, Unwin RJ, Sever PS (1983) Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects. Lancet 2:1225–1227
Nicole P, Lins L, Rouyer-Fessard C, Drouot C, Fulcrand P, Thomas A, Couvineau A, Martinez J, Brasseur R, Laburthe M (2000) Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide. J Biol Chem 275:24003–24012
O’Donnell M, Garippa RJ, O'Neill NC, Bolin DR, Cottrell JM (1991) Structure–activity studies of vasoactive intestinal polypeptide. J Biol Chem 266:6389–6392
O’Donnell M, Garippa RJ, Rinaldi N, Selig WM, Tocker JE, Tannu SA, Wasserman MA, Welton A, Bolin DR (1994) Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis. J Pharmacol Exp Ther 270:1289–1294
Ohmori Y, Maruyama S, Kimura R, Onoue S, Matsumoto A, Endo K, Iwanaga T, Kashimoto K, Yamada S (2004) Pharmacological effects and lung-binding characteristics of a novel VIP analogue, [R15, 20, 21, L17]-VIP-GRR (IK312532). Regul Pept 123:201–207
Ohmori Y, Onoue S, Endo K, Matsumoto A, Uchida S, Yamada S (2006) Development of dry powder inhalation system of novel vasoactive intestinal peptide (VIP) analogue for pulmonary administration. Life Sci 79:138–143
Onoue S, Nagano Y, Tatsuno I, Uchida D, Kashimoto K (1999) Receptor-binding specificity depending on N-terminal structure of VIP/PACAP. Biomed Res 20:219–231
Onoue S, Waki Y, Hamanaka K, Takehiko Y, Kashimoto K (2001a) Vasoactive intestinal peptide regulates catecholamine secretion in rat PC12 cells through the pituitary adenylate cyclase activating polypeptide receptor. Biomed Res 22:77–82
Onoue S, Waki Y, Nagano Y, Satoh S, Kashimoto K (2001b) The neuromodulatory effects of VIP/PACAP on PC-12 cells are associated with their N-terminal structures. Peptides 22:867–872
Onoue S, Endo K, Ohmori Y, Yamada S, Kimura R, Yajima T, Kashimoto K (2004a) Long-acting analogue of vasoactive intestinal peptide, [R15, 20, 21, L17]-VIP-GRR (IK312532), protects rat alveolar L2 cells from the cytotoxicity of cigarette smoke. Regul Pept 123:193–199
Onoue S, Matsumoto A, Nagano Y, Ohshima K, Ohmori Y, Yamada S, Kimura R, Yajima T, Kashimoto K (2004b) Alpha-helical structure in the C-terminus of vasoactive intestinal peptide: functional and structural consequences. Eur J Pharmacol 485:307–316
Onoue S, Ohmori Y, Endo K, Yamada S, Kimura R, Yajima T (2004c) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide attenuate the cigarette smoke extract-induced apoptotic death of rat alveolar L2 cells. Eur J Biochem 271:1757–1767
Onoue S, Ohmori Y, Matsumoto A, Yamada S, Kimura R, Yajima T, Kashimoto K (2004d) Structure-activity relationship of synthetic truncated analogues of vasoactive intestinal peptide (VIP): an enhancement in the activity by a substitution with arginine. Life Sci 74:1465–1477
Onoue S, Yamada S, Yajima T (2007) Bioactive analogues and drug delivery systems of vasoactive intestinal peptide (VIP) for the treatment of asthma/COPD. Peptides 28(9):1640–1650
Pan CQ, Li F, Tom I, Wang W, Dumas M, Froland W, Yung SL, Li Y, Roczniak S, Claus TH, Wang YJ, Whelan JP (2007) Engineering novel VPAC2-selective agonists with improved stability and glucose-lowering activity in vivo. J Pharmacol Exp Ther 320:900–906
Pandol SJ, Dharmsathaphorn K, Schoeffield MS, Vale W, Rivier J (1986) Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP. Am J Physiol 250:G553–G557
Park IY, Park CB, Kim MS, Kim SC (1998) Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus. FEBS Lett 437:258–262
Paul S, Said SI (1987) Characterization of receptors for vasoactive intestinal peptide solubilized from the lung. J Biol Chem 262:158–162
Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH (2003) Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 111:1339–1346
Pozo D (2003) VIP- and PACAP-mediated immunomodulation as prospective therapeutic tools. Trends Mol Med 9:211–217
Rawlings SR, Hezareh M (1996) Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland. Endocr Rev 17:4–29
Riddle MC, Drucker DJ (2006) Emerging therapies mimicking the effects of amylin and glucagon-like peptide 1. Diabetes Care 29:435–449
Rivier J, Spiess J, Thorner M, Vale W (1982) Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature 300:276–278
Robberecht P, De Neef P, Lefebvre RA (1998) Influence of selective VIP receptor agonists in the rat gastric fundus. Eur J Pharmacol 359:77–80
Robinson RM, Blakeney EW Jr., Mattice WL (1982) Lipid-induced conformational changes in glucagon, secretin, and vasoactive intestinal peptide. Biopolymers 21:1271–1228
Rubinstein I, Dagar S, Sethi V, Krishnadas A, Onyuksel H (2001) Liposomal VIP potentiates DNA synthesis in cultured oral keratinocytes. Peptides 22:671–675
Saetrum Opgaard O, Knutsson M, de Vries R, Tom B, Saxena PR, Edvinsson L (2001) Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae. Clin Sci (Lond) 101:637–643
Said SI (1989) Vasoactive intestinal polypeptide and asthma [editorial]. N Engl J Med 320:1271–1273
Said SI (1991) Vasoactive intestinal polypeptide (VIP) in asthma. Ann N Y Acad Sci 629:305–318
Said SI, Mutt V (1970) Polypeptide with broad biological activity: isolation from the small intestine. Science 169:1217–1218
Said SI, Dickman KG (2000) Pathways of inflammation and cell death in the lung: modulation by vasoactive intestinal peptide. Regul Pept 93:21–29
Sakiyama A, Kitada C, Watanabe T, Masuda Y, Fujino M (1991) Structure–activity relationship of pituitary adenylate cyclase activating polypeptide (PACAP). In: Suzuki A (ed) Japanese Peptide Symposium. Protein Research Foundation, Osaka, pp 215–220
Sergejeva S, Hoshino H, Yoshihara S, Kashimoto K, Lotvall J, Linden A (2004) A synthetic VIP peptide analogue inhibits neutrophil recruitment in rat airways in vivo. Regul Pept 117:149–154
Shivers BD, Gorcs TJ, Gottschall PE, Arimura A (1991) Two high affinity binding sites for pituitary adenylate cyclase-activating polypeptide have different tissue distributions. Endocrinology 128:3055–3065
Solano RM, Langer I, Perret J, Vertongen P, Juarranz MG, Robberecht P, Waelbroeck M (2001) Two basic residues of the h-VPAC1 receptor second transmembrane helix are essential for ligand binding and signal transduction. J Biol Chem 276:1084–1088
Stiuso P, Marabotti A, Facchiano A, Lepretti M, Dicitore A, Ferranti P, Carteni M (2006) Assessment of the conformational features of vasoactive intestinal peptide in solution by limited proteolysis experiments. Biopolymers 81:110–119
Suzuki H, Noda Y, Paul S, Gao XP, Rubinstein I (1995) Encapsulation of vasoactive intestinal peptide into liposomes: effects on vasodilation in vivo. Life Sci 57:1451–1457
Takubo T, Banks K, Martin JG (1991) Epithelium modulates the potency of vasoactive intestinal peptide in the guinea pig. J Appl Physiol 71:2146–2151
Tams JW, Jorgensen RM, Holm A, Fahrenkrug J (2000) Creation of a selective antagonist and agonist of the rat VPAC(1) receptor using a combinatorial approach with vasoactive intestinal peptide 6–23 as template. Mol Pharmacol 58:1035–1041
Taylor DP, Pert CB (1979) Vasoactive intestinal polypeptide: specific binding to rat brain membranes. Proc Natl Acad Sci U S A 76:660–664
Thornton K, Gorenstein DG (1994) Structure of glucagon-like peptide (7–36) amide in a dodecylphosphocholine micelle as determined by 2D NMR. Biochemistry 33:3532–3539
Tsutsumi M, Claus TH, Liang Y, Li Y, Yang L, Zhu J, Dela Cruz F, Peng X, Chen H, Yung SL, Hamren S, Livingston JN, Pan CQ (2002) A potent and highly selective VPAC2 agonist enhances glucose-induced insulin release and glucose disposal: a potential therapy for type 2 diabetes. Diabetes 51:1453–1460
Unger RH, Dobbs RE, Orci L (1978) Insulin, glucagon, and somatostatin secretion in the regulation of metabolism. Annu Rev Physiol 40:307–343
Usdin TB, Bonner TI, Mezey E (1994) Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology 135:2662–2680
Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol Rev 52:269–324
Waelbroeck M, Robberecht P, Coy DH, Camus JC, De Neef P, Christophe J (1985) Interaction of growth hormone-releasing factor (GRF) and 14 GRF analogs with vasoactive intestinal peptide (VIP) receptors of rat pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(1–29)-NH2 as a VIP antagonist. Endocrinology 116:2643–2649
Wray V, Kakoschke C, Nokihara K, Naruse S (1993) Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy. Biochemistry 32:5832–5841
Wray V, Nokihara K, Naruse S (1998) Solution structure comparison of the VIP/PACAP family of peptides by NMR spectroscopy. Ann N Y Acad Sci 865:37–44
Wuthrich K (1989) Protein structure determination in solution by nuclear magnetic resonance spectroscopy. Science 243:45–50
Wuthrich K (1998) The second decade—into the third millenium. Nat Struct Biol 5(Suppl):492–495
Xia M, Sreedharan SP, Bolin DR, Gaufo GO, Goetzl EJ (1997) Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor. J Pharmacol Exp Ther 281:629–633
Yajima Y, Akita Y, Saito T, Kawashima S (1998) VIP induces the translocation and degradation of the alpha subunit of Gs protein in rat pituitary GH4C1 cells. J Biochem (Tokyo) 123:1024–1030
Yoshihara S, Yamada Y, Abe T, Kashimoto K, Linden A, Arisaka O (2004) Long-lasting smooth-muscle relaxation by a novel PACAP analogue in human bronchi. Regul Pept 123:161–165
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Onoue, S., Misaka, S. & Yamada, S. Structure-activity relationship of vasoactive intestinal peptide (VIP): potent agonists and potential clinical applications. Naunyn-Schmied Arch Pharmacol 377, 579–590 (2008). https://doi.org/10.1007/s00210-007-0232-0
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DOI: https://doi.org/10.1007/s00210-007-0232-0