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Metabolism and potency of xenin and of its reduced hexapseudopeptide Psi fragment in the dog

机译：犬Xenin及其还原的六肽Psi片段的代谢和效力。

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摘要

Xenin is a 25 amino acid peptide hormone, secreted into the circulation by specific endocrine cells in the duodenal mucosa. Plasma concentrations are elevated after sham feeding and feeding. In the present study the metabolism of xenin and of a C-terminal fragment was investigated. Xenin, its C-terminal hexapeptide, and a pseudopeptide analog Psi (CH2NH) hexapeptide in which a Psi reduced bond is introduced in the biologically important dibasic motif of the C-terminus were infused or injected intravenously in 14 anaesthetized dogs. Plasma disappearance time, metabolic clearance rate, the generation of metabolites, and biological effects on exocrine pancreatic secretion were determined employing radioimmunoassay, high pressure liquid chromatography, mass spectrometry (MALDI-MS), and sequence analysis. Half time after steady state infusion of xenin was 3.1 min(-1) , that of Psi xenin 6 was 6.2(-1) (p < 0.0 1) Plasma concentrations of T xenin 6 were significantly elevated (p < 0.0 1), pancreatic secretion of volume was augmented by a factor of 50, and output of protein by a factor of 30 compared to unmodified xenin 6. MALDI-MS and sequencing after infusion of xenin revealed a C-terminal octapeptide fragment as primary metabolite. Introduction of a reduced pseudobond in the dibasic motif of xenin dramatically enhances biological potency. This indicates that such a reduced pseudopeptide may be useful in the treatment of bowel paralysis. (C) 2003 Elsevier Inc. All rights reserved. [References: 25]
机译：Xenin是一种25个氨基酸的肽激素，由十二指肠粘膜中的特定内分泌细胞分泌到循环系统中。假喂食和喂食后血浆浓度升高。在本研究中，研究了Xenin和C末端片段的代谢。 Xenin，其C端六肽和伪肽类似物Psi（CH2NH）六肽（其中Psi还原键被引入C端生物学上重要的二元基序中）被注入或静脉内注入14只麻醉的狗中。使用放射免疫分析，高压液相色谱，质谱（MALDI-MS）和序列分析确定血浆消失时间，代谢清除率，代谢产物的产生以及对外分泌胰腺分泌的生物学影响。稳定状态下的Xenin输注的半衰期为3.1 min（-1），Psi Xenin 6的半衰期为6.2（-1）（p <0.0 1），血浆T Tenin 6的浓度显着升高（p <0.0 1），胰腺与未修饰的木质素6相比，分泌的体积增加了50倍，蛋白质输出增加了30倍。MALDI-MS和输注木质素后的测序表明，C端八肽片段为主要代谢产物。在木质素的二元基序中引入还原的假键可显着增强生物学效能。这表明这种减少的假肽可能在肠麻痹的治疗中有用。 （C）2003 Elsevier Inc.保留所有权利。 [参考：25]

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