Ex vivo method for determining potential GLP-2 receptor modulators

摘要

Disclosed herein is a method for measuring the contractility of intestinal tissue upon treatment with GLP-2 or a GLP-2 ligand. Also disclosed is an assay which directly measures the activity of GLP-2 or GLP-2 ligands ex vivo and permits the screening of putative GLP-2 ligands in native tissue.

主权项

1. A method for determining a relative ability of different compounds to potentially modulate glucagon-like peptide-2 (GLP-2) receptor activity in intestine comprising the steps of:
i. incubating a first ex vivo intestinal tissue segment with a GLP-2 receptor ligand; ii. taking a first measurement of contractility of the first ex vivo intestinal tissue segment; iii. incubating the first ex vivo intestinal tissue segment with the GLP-2 receptor ligand and a first compound; iv. taking a second measurement of contractility of the first ex vivo intestinal tissue segment; v. incubating a second ex vivo intestinal tissue segment with the GLP-2 receptor ligand; vi. taking a first measurement of contractility of the second ex vivo intestinal tissue segment; vii. incubating the second ex vivo intestinal tissue segment with the GLP-2 receptor ligand and a second compound; viii. taking a second measurement of contractility of the second ex vivo intestinal tissue segment; and ix. comparing a difference between the first and the second measurements of contractility of the first ex vivo intestinal tissue segment with a difference between the first and second measurements of contractility of the second ex vivo intestinal tissue segment;wherein a result of comparing the difference between the first and second measurements of contractility of the first ex vivo intestinal tissue segment with the difference between the first and second measurements of contractility of the second ex vivo intestinal tissue segment is indicative of the relative abilities of the compounds to potentially modulate GLP-2 receptor activity.