Structure-activity relationship of synthetic truncated analogues of vasoactive intestinal peptide (VIP): an enhancement in the activity by a substitution with arginine

Onoue, Satomi; Ohmori, Yuki; Matsumoto, Asako; Yamada, Shizuo; Kimura, Ryohei; Yajima, Takeaki; Kashimoto, Kazuhisa

doi:10.1016/j.lfs.2003.07.048

Cited by 14 publications

(23 citation statements)

References 32 publications

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“…L2 cells maintained the shape of type II alveolar pneumonocytes and retained the phenotype and functions of type II cells, including differentiation, synthesis of various endogenous compounds, and expression of specific receptors [37]. In the present study, the RT-PCR experiment revealed the exclusive expression of VPAC2 receptors in L2 cells, and this is consistent with our previous study which showed a predominant expression of the VPAC2 receptor in rat lung [38]. Furthermore, the radioligand-binding assay, with 125 I-labelled VIP, demonstrated the existence of high-affinity and saturable 125 Ilabelled VIP-binding sites in L2 cells, as revealed by the K d (0.77 · 10 )9 M) and B max (725 · 10 )15 molAEmg )1 of protein) values.…”

Section: Discussionsupporting

confidence: 92%

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Onoue

Ohmori

Endo

et al. 2004

European Journal of Biochemistry

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Chronic obstructive pulmonary disease is a major clinical disorder usually associated with cigarette smoking. A central feature of chronic obstructive pulmonary disease is inflammation coexisting with an abnormal protease/antiprotease balance, leading to apoptosis and elastolysis. In an in vitro study of rat lung alveolar L2 cells, cigarette smoke extract (CSE) induced apoptotic cell death. Exposure of L2 cells to CSE at a concentration of 0.25% resulted in a 50% increase of caspase-3 and matrix metalloproteinase (MMP) activities. Specific inhibitors for caspases and MMPs attenuated the cytotoxicity of CSE. RT-PCR amplification identified VPAC2 receptors in L2 cells. A radioligand-binding assay with 125 I-labeled vasoactive intestinal peptide (VIP) found high affinity and saturable 125 I-labeled VIP-binding sites in L2 cells. VIP and pituitary adenylate cyclase-activating polypeptide (PACAP27) were approximately equipotent for both VIP receptor binding and stimulation of cAMP production in L2 cells. Both neuropeptides, at concentrations higher than 10 )13 M, produced a concentration-dependent inhibition of CSE-induced cell death in L2 cells. VIP, at 10 )7 M, reduced CSE-stimulated MMP activity and caspase-3 activation. The present study has shown that VIP and PACAP27 significantly attenuate the cytotoxicity of CSE through the activation of VPAC2 receptor, and the protective effect of VIP may partly be the result of a reduction in the CSE-induced stimulation of MMPs and caspases.

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Section: Discussionsupporting

confidence: 92%

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Onoue

Ohmori

Endo

et al. 2004

European Journal of Biochemistry

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“…VIP is a 28-amino-acid peptide, a member of the secretin/glucagon superfamily, which acts on G proteincoupled receptors [96]. Despite its proposed role in protein extravasation, current studies have questioned its role in migraine pathogenesis.…”

Section: Vasoactive Intestinal Peptidementioning

confidence: 99%

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Lukács

Tajti

Fülöp

et al. 2017

CMC

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Abstract:Background: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms. Objective: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation. Method: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published in January 2017. Results: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant result compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC 1 ), and kynurenic acid (KYNA) analogues. Conclusion: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

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“…All chemicals and solvents, unless otherwise specified, were of analytical grade and were used without purification. VIP and [R 8,15,21 , L 17 ]-VIP (in purities of >91%) were supplied by GL Biochemical Corp. (Shanghai, China). High-performance liquid chromatography (HPLC) was carried out on a system consisting of a P680 pump, a PDA-100 photodiode array detector and a NaI(Tl) scintillation detector, with the column being LiChrosorb C18 (10 lm, 300 · 3.9 mm).…”

Section: Generalmentioning

confidence: 99%

“…In this study, [R 8,15,21 , L 17 ]-VIP (Scheme 1B) was designed with the replacement of Asp8, Lys15, Lys21 by Arg and Met17 by Leu in amino acids sequence of VIP, as it is suitable for 18 F-labeling and has good proteolytic stability and high receptor-binding activity. For further investigation, [ 18 F]FB-[R 8,15,21 , L 17 ]-VIP was synthesized by conjugating [ 18 F]SFB with e-amino group of Lys20 ( Figure 1). Our aim was to determine whether the resulting [ 18 F]FB-[R 8,15,21 , L 17 ]-VIP would have the required pharmacokinetic properties to permit the binding and imaging of VIP receptors in vivo.…”

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confidence: 99%

Radiolabeling and in vitro and in vivo Characterization of [¹⁸F]FB‐[R^8,15,21, L¹⁷]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors

Cheng

Yin²,

et al. 2006

Chem Biol Drug Des

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In an effort to develop a peptide-based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R 8,15,21 ]-VIP from non-target tissues and specific uptakes by tumors realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [ Vasoactive intestinal peptide (VIP, Scheme 1A), with a wide range of biologic activities, was extracted from porcine duodenum previously by Said and Mutt (1). It was found that biologic effects of VIP are mediated through interactions with a large family of G-protein-coupled receptors in cell membrane. Two receptor subclasses named VPAC1 and VPAC2, are expressed in a number of normal tissues, such as lung, liver, gastrointestinal tract, and peripheral blood vessels (2-7), and that many tumor cells, such as neuroendocrine tumors, brain tumors, and adenocarcinomas of colon, pancreas, stomach, and liver, contain high-density VIP receptors (8). Therefore, radiolabeled VIP is a preferable agent for imaging gastrointestinal and neuroendocrine tumors (9).Since 1994, however, the argument about detection efficiency of this compound remained unclarified, which could be related to fast proteolytic degradation of VIP in vivo and, as a result, the radioactivity uptakes in tumor might be too low to distinguish small tumors, even to cause false-negative results (7,(10)(11)(12). A VIP analog with longer half-life of proteolytic degradation and higher receptor-binding affinities, nevertheless, would need chemical modifications of the VIP. Therefore, 99m Tc-labeled structure-modified VIP analogs of VIP-AbaGly-Gly-(D)-Ala-Gly (TP3654) and [des-Met17,S-(CH 2 CO-Gly-Gly-CysLys-amide) Hcy17] VIP (P1666), with longer half-life of proteolytic degradation and high receptor-binding affinities, are promising agents for localizing tumor-expressing VIP receptors, and are used for single photon emission computed tomography imaging (SPECT; 13-15).Positron emission tomography (PET), an imaging technique with 18 F or other positron emission radionuclides, is more powerful than computed tomography (CT), magnetic resonance imaging (MRI) and SPECT for early detection of carcinomas, hence higher cure rate than tumors diagnosed in advanced stage (16,17). Therefore, labeling VIP with 18

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Structure-activity relationship of synthetic truncated analogues of vasoactive intestinal peptide (VIP): an enhancement in the activity by a substitution with arginine

Cited by 14 publications

References 32 publications

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Radiolabeling and in vitro and in vivo Characterization of [¹⁸F]FB‐[R^8,15,21, L¹⁷]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors

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Structure-activity relationship of synthetic truncated analogues of vasoactive intestinal peptide (VIP): an enhancement in the activity by a substitution with arginine

Cited by 14 publications

References 32 publications

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide attenuate the cigarette smoke extract‐induced apoptotic death of rat alveolar L2 cells

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Radiolabeling and in vitro and in vivo Characterization of [18F]FB‐[R8,15,21, L17]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors

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Radiolabeling and in vitro and in vivo Characterization of [¹⁸F]FB‐[R^8,15,21, L¹⁷]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors