Bombesin-like peptides stimulate growth hormone secretion mediated by the gastrin-releasing peptide receptor in cattle

Zhao, Hongqiong; Matsuda, Seinosuke; ThanThan, S.; Yannaing, S.; Kuwayama, Hideto

doi:10.1016/j.peptides.2012.07.018

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…Although it was predicted that the replacement of Leu 3 in NMB by His 3 in NMC would hinder the acquisition of a helical membrane-bound structure, 20 we have shown that the Cterminal region of NMC folds into an a-helix upon micelle insertion, whereas the N-terminal segment remains unstructured. This folding process must be directly related to the energetically favoured insertion of Trp 4 , Val 6 , Gly 7 , Leu 9 and Met 10 (residues with a DG < 0 of transfer form water to lipid bilayers 40 ) into the non-polar micelle, which was experimentally observed through intermolecular NOEs (Fig. 5B).…”

Section: Discussionmentioning

confidence: 82%

“…7 NMC can also reduce the appetite, and therefore can act as a anorexia inducer, 8 likely through its interaction with bombesin receptors in the central amygdala. 9 In addition, its intravenous administration increases growth hormone levels in calves, 10 while it can also act as an autocrine growth factor in human small-cell lung cancer. 11 Moreover, NMC has been shown to regulate growth and/or differentiation of human tumors in a wide range of tissues, including carcinomas of pancreas, stomach, breast, prostate and colon.…”

Section: Introductionmentioning

confidence: 99%

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Conformational ensembles of neuromedin C reveal a progressive coil-helix transition within a binding-induced folding mechanism

et al. 2015

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Abstract:Neuromedin C (NMC) is a peptide that regulates various processes in the central nervous system and gastrointestinal tract through its interaction with the bombesin receptor subtype-2 (BB2R). Hence, BB2R antagonists hold potential to treat disorders that occur as a result of NMC dysfunction or misregulation. However, their efficient design requires a detailed understanding of the structural features of NMC, which hitherto are unknown. Here we describe the conformational ensembles of NMC in aqueous solution, at five different TFE concentrations to decode its folding pathway, and under its SDS micelle bound state that likely resembles the receptor-triggered conformation. NMC displays a disordered but well-defined backbone architecture that undergoes a progressive coil-helix transition with increasing TFE concentrations, first at the C-terminus and then at the N-terminus. NMC also adopts a C-terminal α-helical conformation upon binding to SDS micelles. This micelle binding is directed by hydrophobic interactions that concur with the unfavorable deprotonation of His8 and its further insertion into the micelle. Moreover, NMR relaxation data reveal that the acquisition of the micelle bound α-helical conformation constrains the NMC flexibility more than the confinement itself. This comprehensive study of the structural behavior of NMC provides essential mechanistic information for the development of new Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationtherapeutics to treat neurological, cancer-related or eating disorders.Author Comments: Dear Editor,We would like to submit our manuscript entitled "Conformational ensembles of neuromedin C reveal a progressive coil-helix transition within a binding-induced folding mechanism" to be considered for publication in Chemistry A-European Journal.Neuromedin C (NMC) is a decapeptide that regulates different biological process in the central nervous system and in the gastrointestinal tract. For instance, NMC modulates appetite, participates in neurotransmission, and regulates growth and differentiation of tumors. All these processes are mediated through its interaction with the subtype-2 bombesin receptor (BB2R), which is a member of the G-protein coupled receptor superfamily. Thus, BB2R antagonists are considered as potential therapeutics and their efficient design will benefit from the understanding of the structural features of NMC.At present, the available structural information on NMC is very limited. Therefore, we provide a comprehensive description of the structural behavior of NMC in the accompanying manuscript. Different biophysical techniques (nuclear magnetic resonance, fluorescence, circular dichroism and isothermal titration calorimetry) were used to characterize the conformations of NMC in aqueous solution. We calculated the solution structure of NMC at increasing TFE concentrations in order to describe at residue level the pathway involved in its coil-helix transition, a process that likely mimics the receptor interaction. T...

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Conformational ensembles of neuromedin C reveal a progressive coil-helix transition within a binding-induced folding mechanism

et al. 2015

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“…Besides GHRH (analogs) and GHRPs, other GH‐secretion stimulating compounds for cattle, such as somatotropin‐like peptide (PEP‐ST), a 27 amino acid long polypeptide of 3,022 Da, have been reported (Gallo et al, ). In addition, recent studies demonstrated the stimulation of GH secretion in cattle with gastrin (Zhao et al, ) and the bombesin‐like peptide neuromedin C (Zhao et al, ).…”

Section: Peptides and Proteins With Growth‐promoting Propertiesmentioning

confidence: 99%

Current trends in mass spectrometry of peptides and proteins: Application to veterinary and sports‐doping control

Broek

Blokland

Nessen

et al. 2013

Mass Spectrometry Reviews

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Detection of misuse of peptides and proteins as growth promoters is a major issue for sport and food regulatory agencies. The limitations of current analytical detection strategies for this class of compounds, in combination with their efficacy in growth-promoting effects, make peptide and protein drugs highly susceptible to abuse by either athletes or farmers who seek for products to illicitly enhance muscle growth. Mass spectrometry (MS) for qualitative analysis of peptides and proteins is well-established, particularly due to tremendous efforts in the proteomics community. Similarly, due to advancements in targeted proteomic strategies and the rapid growth of protein-based biopharmaceuticals, MS for quantitative analysis of peptides and proteins is becoming more widely accepted. These continuous advances in MS instrumentation and MS-based methodologies offer enormous opportunities for detection and confirmation of peptides and proteins. Therefore, MS seems to be the method of choice to improve the qualitative and quantitative analysis of peptide and proteins with growth-promoting properties. This review aims to address the opportunities of MS for peptide and protein analysis in veterinary control and sports-doping control with a particular focus on detection of illicit growth promotion. An overview of potential peptide and protein targets, including their amino acid sequence characteristics and current MS-based detection strategies is, therefore, provided. Furthermore, improvements of current and new detection strategies with state-of-the-art MS instrumentation are discussed for qualitative and quantitative approaches.

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Insulinotropic action of bombesin-like peptides mediated by gastrin-releasing peptide receptors in steers1

Zhao

Yao

Yannaing

et al. 2016

Journal of Animal Science

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The present study characterizes the receptor that mediates the insulinotropic action of bombesin-like peptides (BLP) in ruminants. Eight Holstein steers were randomly and intravenously injected with synthetic bovine gastrin-releasing peptide (GRP; 0.9 nmol/kg BW), neuromedin B (NMB; 0.9 nmol/kg BW), or neuromedin C (NMC; 0.9 nmol/kg BW), each alone or combined with the antagonist of GRP receptors N-acetyl-GRP-OCHCH (N-GRP-EE; 22.5 nmol/kg BW) or the antagonist of GH secretagogue receptor type 1a (GHS-R1a) [D-Lys]-GHRP-6 (21.5 nmol/kg BW). Blood samples were collected at -10, 0 (just before injection), 5, 10, 15, 20, 30, 45, 60, 75, and 90 min relative to injection time. Levels of injected peptides, insulin, and glucose in plasma were analyzed. Results showed that the peak of insulin levels was seen at 5 min after injection of NMC or GRP. Plasma glucose was observed in 2 phases; a significant rise followed a remarkable fall after NMC or GRP administration compared with injection of the vehicle ( < 0.05). On a same molar basis, effects of GRP on insulin and glucose were more potent than those of NMC ( < 0.05). The NMC-induced changes of insulin and glucose were completely blocked by N-GRP-EE, but [D-Lys]-GHRP-6 did not block any of these changes. Administration of NMB or N-GRP-EE alone did not change the circulating levels of insulin or glucose during any of the sampling time points ( > 0.05). These results indicated that the insulinotropic action of BLP is mediated by GRP receptors but not through a ghrelin/GHS-R1a pathway and that BLP may be involved in the regulation of glucose homeostasis in ruminants.

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Bombesin-like peptides stimulate growth hormone secretion mediated by the gastrin-releasing peptide receptor in cattle

Cited by 3 publications

References 37 publications

Conformational ensembles of neuromedin C reveal a progressive coil-helix transition within a binding-induced folding mechanism

Conformational ensembles of neuromedin C reveal a progressive coil-helix transition within a binding-induced folding mechanism

Current trends in mass spectrometry of peptides and proteins: Application to veterinary and sports‐doping control

Insulinotropic action of bombesin-like peptides mediated by gastrin-releasing peptide receptors in steers1

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