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Title: Binding sites for progastrin-derived peptides in colonic crypts.
Austin Authors: Karelina, Y;Baldwin, Graham S
Affiliation: University Department of Surgery, Austin Hospital, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia
Issue Date: 1-Feb-2001
Publication information: Journal of Gastroenterology and Hepatology; 16(2): 169-75
Abstract: Gastrin17gly acts as a growth factor for the colonic mucosa. Studies on the binding properties of the receptor involved in transducing the proliferative effects have generally been confined to colorectal carcinoma cell lines, and no investigation of gastrin17gly receptors on normal colonocytes has yet been reported. The aim of this study was to investigate the binding of 125I-[Met15]-gastrin17gly to normal colonic crypts.Crypts were released from normal rat and rabbit colonic mucosa by treatment with EDTA and isolated by centrifugation. The binding of 125I-[Met15]-gastrin17gly was measured in displacement experiments with increasing concentrations of either gastrin17gly, gastrin17 or gastrin receptor antagonists. The concentrations required for 50% inhibition were determined by the use of curve fitting.125I-[Met15]-Gastrin17gly bound to both rat and rabbit crypts, and displacement experiments with unlabeled gastrin17gly revealed that the IC50 values were 1.0 +/- 0.6 and 0.6 +/- 0.2 micromol/L, respectively. Binding was also competed by gastrin17, with IC50 values of 2.4 +/- 1.7 and 2.4 +/- 0.7 micromol/L, respectively. Binding was inhibited by the non-selective gastrin/CCK receptor antagonists proglumide and benzotript, but not by the cholecystokinin (CCK)-A receptor antagonist L364 718, or the gastrin/CCK-B receptor antagonist L365 260.We conclude that the gastrin17gly binding site on normal colonic crypts has properties consistent with the gastrin/CCK-C receptor.
Gov't Doc #: 11207897
Type: Journal Article
Subjects: Animals
Binding Sites
Chromatography, High Pressure Liquid
Intestinal Mucosa.chemistry
Models, Animal
Protein Precursors.metabolism
Receptors, Cholecystokinin.antagonists & inhibitors
Appears in Collections:Journal articles

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