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Binding sites for progastrin‐derived peptides in colonic crypts
Author(s) -
Karelina Yulia,
Baldwin Graham S
Publication year - 2001
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2001.02429.x
Subject(s) - proglumide , gastrin , receptor , cholecystokinin , endocrinology , antagonist , medicine , receptor antagonist , cholecystokinin receptor , binding site , biology , biochemistry , secretion
Background and Aims: Gastrin 17 gly 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 gastrin 17 gly receptors on normal colonocytes has yet been reported. The aim of this study was to investigate the binding of 125 I‐[Met 15 ]‐gastrin 17 gly to normal colonic crypts. Methods: Crypts were released from normal rat and rabbit colonic mucosa by treatment with EDTA and isolated by centrifugation. The binding of 125 I‐[Met 15 ]‐gastrin 17 gly was measured in displacement experiments with increasing concentrations of either gastrin 17 gly, gastrin 17 or gastrin receptor antagonists. The concentrations required for 50% inhibition were determined by the use of curve fitting. Results: 125 I‐[Met 15 ]‐Gastrin 17 gly bound to both rat and rabbit crypts, and displacement experiments with unlabeled gastrin 17 gly revealed that the IC 50 values were 1.0 ± 0.6 and 0.6 ± 0.2 μmol/L, respectively. Binding was also competed by gastrin 17 , with IC 50 values of 2.4 ± 1.7 and 2.4 ± 0.7 μmol/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. Conclusion: We conclude that the gastrin 17 gly binding site on normal colonic crypts has properties consistent with the gastrin/CCK‐C receptor.