Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9420
Title: Metabolism of recombinant progastrin in sheep.
Authors: Paterson, Adrienne C;Baldwin, Graham S;Shulkes, Arthur
Affiliation: Department of Surgery, University of Melbourne, Austin, and Repatriation Medical Centre, Melbourne, Victoria 3084, Australia.
Issue Date: 1-Sep-2002
Citation: American Journal of Physiology. Endocrinology and Metabolism; 283(3): E449-56
Abstract: Precursor forms of peptide hormones may be biologically active with effects distinct from the mature end product. Nonamidated progastrin-derived peptides stimulate growth of colonic epithelium and are elevated in the circulation of patients with colorectal carcinomas, whereas the amidated end product is the major regulator of gastric acidity. Using region-specific radioimmunoassays, we here compared the in vitro and in vivo metabolism of recombinant human progastrin-(6-80) and two other nonamidated gastrins, gastrin-17-Gly and Tyr(70)-progastrin-(71-80). Although progastrin-(6-80) was very stable in vitro, both progastrin-(6-80) and gastrin-17-Gly were degraded in vivo. The in vivo data were best fitted by a double-exponential decay curve, and the half-lives for progastrin-(6-80) (t1/2alpha = 5.1 +/- 1.1, t(1/2)beta = 42 +/- 11 min) were significantly (P < 0.05) longer than for gastrin-17-Gly (t(1/2)alpha = 2.2 +/- 0.6, t(1/2)beta = 13 +/- 1 min). Tyr(70)-progastrin-(71-80) was degraded more rapidly. Comparison with amidated gastrins suggests that peptide length, rather than sequence, is the critical determinant of clearance. Progastrin has the clearance characteristics to be considered a circulating hormone.
Internal ID Number: 12169437
URI: http://ahro.austin.org.au/austinjspui/handle/1/9420
DOI: 10.1152/ajpendo.00042.2002
URL: http://www.ncbi.nlm.nih.gov/pubmed/12169437
Type: Journal Article
Subjects: Animals
Gastrins.blood.chemistry
Humans
Peptide Fragments.blood
Protein Precursors.blood.chemistry
Recombinant Proteins.blood
Sheep
Appears in Collections:Journal articles

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