Journal article

Publication year: 2003

Pages: 697-707

Journal: Life Sciences

Volume number: 74

Issue number: 6

ISSN: 0024-3205

DOI Link: https://doi.org/10.1016/j.lfs.2003.05.009

Publisher: Elsevier

Abstract: 
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<0.01) Plasma concentrations of psi xenin 6 were significantly elevated (p<0.01), 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.

Harvard Citation style: Feurle, G., Meyer, H. and Hamscher, G. (2003) Metabolism and potency of xenin and of its reduced hexapseudopeptide Ψ fragment in the dog, Life Sciences, 74(6), pp. 697-707. https://doi.org/10.1016/j.lfs.2003.05.009

APA Citation style: Feurle, G., Meyer, H., & Hamscher, G. (2003). Metabolism and potency of xenin and of its reduced hexapseudopeptide Ψ fragment in the dog. Life Sciences. 74(6), 697-707. https://doi.org/10.1016/j.lfs.2003.05.009