Action of exendin (9-39) amide on GLP-1 (7-36) amide and exendin-4 mediated contractions of Suncus murinus (house musk shrew) isolated ileum

Abstract

In the present studies, we investigated the action of glucagon-like peptide (GLP-1) agonists GLP-1 (7-36) amide and exendin-4 on the Suncus murinus isolated ileum. Segments of ileumwere placed in an organ bath containing Kreb’s solution. Agonists were added to the bath using a 2-6 min dosing schedule. GLP-1 (7-36) amide and exendin-4 (0.1-100 nM) induced concentration-dependent contractions yielding pEC₅₀ values of 8.6 ±0.3 and 8.3 ±0.3, respectively. The GLP-1 antagonist exendin (9-39) amide (0.3-3 nM) was inactive alone, but non-competitively antagonized the action of both agonists with apparent pK_B values of 9.8 and 9.7, respectively. In other experiments, tetrodotoxin (1 μM) and atropine (1 μM) significantly antagonized (p < 0.01) the contractile action of exendin-4 (10 nM), whereas hexamethonium (500 μM) had no action. In conclusion, the action of GLP-1 receptor agonists to contract the ileum probably involves the enteric nervous system and a release of acetylcholine to activate muscarinic receptors.