Bombesin effects on human GI functions

Fave, Gianfranco Delle; Annibale, Bruno; Magistris, Laura de; Severi, Carola; Bruzzone, Roberto; Puoti, M.; Melchiorri, Pietro; Torsoli, A; Erspamer, V.

doi:10.1016/0196-9781(85)90360-2

Cited by 40 publications

(28 citation statements)

References 12 publications

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“…The reason for this dis crepancy is unknown. In humans, exogenous BBN, administered as an intravenous infu sion, resulted in elevated scrum levels of amy lase and lipase [21], In the present study, the increase in amylase activity was greatest at the lowest dose of BBN (1.25 pg/kg), and was observed whether activities were calculated as units/total pancreas or as a function of protein or DNA. Thus, increased amylase activity was not due simply to an increase in pan creatic mass or cell number, but represented a true induction of enzyme activity.…”

Section: Discussionmentioning

confidence: 65%

Evidence of a Physiological Role for Bombesin in the Postnatal Development of the Rabbit Pancreas

Karkashan¹,

MacNaughton²,

Gall³

1992

Neonatology

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The effect of chronic administration of bombesin (BBN) on the development of the pancreas and the role of endogenous BBN in the postnatal development of exocrine pancreatic function were investigated in suckling New Zealand White rabbits. BBN administered intraperitoneally (i.p) at various doses (1.25,12.5 and 30 µg/kg body weight) to suckling rabbits for 13 days starting on day 4 of life induced pancreatic growth as characterized by dose-dependent increases in pancreatic wet weight, total protein content and total DNA content compared to littermate controls. The maximum effect was observed using bombesin at 30 µg/kg. This increase represented hyperplasia since there was no BBN-induced change in the protein:DNA ratio. Pancreatic amylase activity was significantly increased by all doses of BBN, with a maximal effect at 1.25 µg/kg. The specific BBN receptor antagonist [Leu¹³-ψ(CH₂NH)Leu¹⁴]-BBN, given i.p for 9 days at 30 µg/kg body weight starting on day 20 of life, significantly reduced the development of pancreatic amylase and lipase activities compared to controls (48 and 36% reductions, respectively). Our findings confirm the trophic effect of BBN on the neonatal pancreas and provide evidence of a physiological role for endogenous BBN-peptides in the development of pancreatic exocrine function.

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Section: Discussionmentioning

confidence: 65%

Evidence of a Physiological Role for Bombesin in the Postnatal Development of the Rabbit Pancreas

Karkashan¹,

MacNaughton²,

Gall³

1992

Neonatology

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“…Bombesin and its mammalian counterparts gastrin-releasing peptide (GRP) and neuromedin B (NMB) elicit a wide spectrum of biological responses in mammalian tissues, including the central nervous system and the gut [2,3,4]. Bombesin-like peptides exert their effects on target cells by binding to surface G protein-coupled receptors characterized by the typical configuration of seven transmembrane domains [5].…”

Section: Introductionmentioning

confidence: 99%

[99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging

Nock

Nikolopoulou

Chiotellis

et al. 2003

Eur J Nucl Med Mol Imaging

172

184

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Demobesin 1 is a potent new GRP-R-selective bombesin (BN) analogue containing an open chain tetraamine chelator for stable technetium-99m binding. Following a convenient labelling protocol, the radiopeptide, [(99m)Tc]Demobesin 1, formed in nearly quantitative yields and with high specific activities. Both unlabelled and labelled peptide demonstrated high-affinity binding in membrane preparations of the human androgen-independent prostate adenocarcinoma PC-3 cell line. The IC(50) values determined for Demobesin 1 and [Tyr(4)]BN were 0.70+/-0.08 n M and 1.5+/-0.20 n M, respectively, while the K(d) defined for [(99m)Tc/(99g)Tc]Demobesin 1 was 0.67+/-0.10 n M. [(99m)Tc]Demobesin 1 was rather stable in murine plasma, whereas it degraded rapidly in kidney and liver homogenates. After injection in healthy Swiss albino mice, [(99m)Tc]Demobesin 1 accumulated very efficiently in the target organs (pancreas, intestinal tract) via a GRP-R-mediated process, as shown by in vivo receptor blocking experiments. An equally high and GRP-R-mediated uptake was exhibited by [(99m)Tc]Demobesin 1 after injection in PC-3 tumour-bearing athymic mice. The initial high radioligand uptake of 16.2+/-3.1%ID/g in the PC-3 xenografts at 1 h p.i. remained at a similar level (15.61+/-1.19%ID/g) at 4 h p.i. Even after 24 h p.i., when the radioactivity had cleared from all other tissues, a value of 5.24+/-0.67%ID/g was still observed in the tumour. The high and prolonged localization of [(99m)Tc]Demobesin 1 at the tumour site and its rapid background clearance are very promising qualities for GRP-R-targeted tumour imaging in man.

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“…BBN, a 14-amino acid-potent GRPR agonist found in the skin of the fire-bellied toad Bombina bombina , was first described by Anastasi et al [17]. BBN is involved in regulating exocrine secretion, smooth muscle contraction and gastrointestinal hormone release [18], and it is widely expressed in the central nervous system [19]. [D-Tyr 6 ,βAla 11 , Thi 13 , Nle 14 ]BBN(6-14) [BBN(6-14)] is a potent modified GRPR agonist peptide that binds to GRPR with high affinity [20].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of 64Cu/NOTA-[D-Tyr6,βAla11,Thi13,Nle14]BBN(6-14) monomer and dimers for prostate cancer PET imaging

et al. 2012

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BackgroundGastrin-releasing peptide receptors [GRPR] are highly over-expressed in multiple cancers and have been studied as a diagnostic target. Multimeric gastrin-releasing peptides are expected to have enhanced tumor uptake and affinity for GRPR. In this study, a 64Cu-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid [NOTA]-monomer and two NOTA-dimers of [D-Tyr6,βAla11, Thi13, Nle14]bombesin(6-14) ] [BBN(6-14)] were compared.MethodsMonomeric and dimeric peptides were synthesized on solid phase support and radiolabeled with 64Cu. NOTA-dimer 1 consists of asymmetrically linked BBN(6-14), while NOTA-dimer 2 has similar spacer between the two BBN(6-14) ligands and the chelator. In vitro GRPR-binding affinities were determined with competitive binding assays on PC3 human prostate cancer cells. In vivo stability and biodistribution of radiolabeled compounds were assessed in Balb/c mice. Cellular uptake and efflux were measured with radiolabeled NOTA-monomer and NOTA-dimer 2 on PC3 cells for up to 4 h. In vivo biodistribution kinetics were measured in PC3 tumor-bearing Balb/c nude mice by μ-positron emission tomography [μPET] imaging and confirmed by dissection and counting.ResultsNOTA-monomer, NOTA-dimers 1 and 2 were prepared with purity of 99%. The inhibition constants of the three BBN peptides were comparable and in the low nanomolar range. All 64Cu-labeled peptides were stable up to 24 h in mouse plasma and 1 h in vivo. 64Cu/NOTA-dimer 2 featuring a longer spacer between the two BBN(6-14) ligands is a more potent GRPR-targeting probe than 64Cu/NOTA-dimer 1. PC3 tumor uptake profiles are slightly different for 64Cu/NOTA-monomer and 64Cu/NOTA-dimer 2; the monomeric BBN-peptide tracer exhibited higher tumor uptake during the first 0.5 h and a fast renal clearance resulting in higher tumor-to-muscle ratio when compared to 64Cu/NOTA-dimer 2. The latter exhibited higher tumor-to-blood ratio and was retained longer at the tumor site when compared to 64Cu/NOTA-monomer. Lower ratios of tumor-to-blood and tumor-to-muscle in blocking experiments showed GRPR-dependant tumor uptake for both tracers.ConclusionBoth 64Cu/NOTA-monomer and 64Cu/NOTA-dimer 2 are suitable for detecting GRPR-positive prostate cancer in vivo by PET. Tumor retention was improved in vivo with 64Cu/NOTA-dimer 2 by applying polyvalency effect and/or statistical rebinding.

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Bombesin effects on human GI functions

Cited by 40 publications

References 12 publications

Evidence of a Physiological Role for Bombesin in the Postnatal Development of the Rabbit Pancreas

Evidence of a Physiological Role for Bombesin in the Postnatal Development of the Rabbit Pancreas

[99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging

Comparative study of 64Cu/NOTA-[D-Tyr6,βAla11,Thi13,Nle14]BBN(6-14) monomer and dimers for prostate cancer PET imaging

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