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Title: Pharmacokinetics and organ specific metabolism of glycine-extended and amidated gastrin in sheep.
Austin Authors: Ciccotosto, Graham D;Shulkes, Arthur
Affiliation: Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia
Issue Date: 1-Nov-1992
Publication information: The American Journal of Physiology; 263(5 Pt 1): G802-9
Abstract: Glycine (Gly)-extended gastrin has been described as the inactive precursor form of the biologically active amidated gastrin. The ratio of Gly-extended to amidated gastrin is higher in the circulation than in tissue, suggesting either differential secretion and/or metabolism. Although the distribution of the precursor form is similar in tissue and circulation to its amidated product, the significance of measurable levels of precursor peptide in the circulation is unknown. In this study, we have examined the pharmacokinetic properties and organ-specific metabolism of both the Gly-extended and the amidated forms of gastrin-17 (G-17-Gly and G-17-amide) in the conscious sheep. The metabolic clearance rate, half disappearance time, and production rates were similar for both G-17-Gly and G-17-amide. G-17-Gly was extracted across the head, kidney, and lung but not across the gut and liver. Similarly, G-17-amide was extracted across the head, gut, lung, and kidney but not across the liver. G-17-Gly had no biological activity as evidenced by its failure to stimulate somatostatin secretion nor was there any measurable conversion to amidated gastrin in the circulation. We conclude that the presence of G-17-Gly in the circulation is not the result of a slower clearance and that circulating G-17-Gly is not a precursor for circulating gastrin-amide. The results of this study provide important baseline data for understanding the dynamics of the precursor product relationship between G-Gly and G-amide.
Gov't Doc #: 1359796
Journal: American Journal of Physiology
Type: Journal Article
Subjects: Amino Acid Sequence
Carotid Arteries
Chromatography, High Pressure Liquid
Molecular Sequence Data
Portal Vein
Tissue Distribution
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