Glicentin (proglucagon 1-69 GLIC) and oxyntomodulin (proglucagon 33-69 or OXM) are two peptide hormones that are co-released from ileum and large intestine during digestion. They modulate in vivo gastric acid secretion and the gastro-pyloro-duodenal activity. The specificity of their effects is linked to the presence of their C-terminal octapepide. As yet, no isolated target cell that responds specifically to this family of peptides has been described. The present report describes the in vitro effect of human synthetic GLIC, OXM and octapeptide-bearing fragments on smooth muscle cells isolated from the rabbit antrum. GLIC or OXM decreased the mean length of the cells by: 13.9 +/- 0.8% and 15.5 +/- 0.9%, respectively - GLIC being 16 times more potent than OXM (respective EC50 values: 5 and 83 pM). The C-terminal fragments OXM(19-37) and OXM(30-37) were as efficient as GLIC or OXM. Their potencies were OXM = OXM(19-37)>>OXM(30-37). Glucagon, which corresponds to OXM without the C-terminal octapeptide, or glucagon-like peptide-1 (7-36 amide) did not have any effect. The response to OXM was not influenced by antagonists to muscarinic, cholecystokinin or substance P receptors. In conclusion, our studies demonstrate for the first time an isolated target cell that responds specifically to GLIC, OXM and other octapeptide-bearing peptides.