Activity of oxyntomodulin on gastric acid secretion induced by histamine or a meal in the rat

Conscious rats with chronic gastric fistula were trained for drinking a 14-ml milk meal. The activity of an intestinal hormone, oxyntomodulin (OXM), was studied in this model and compared to that observed when histamine was the stimulus. Under histamine (0.25 mg.kg-1.h-1) stimulation, OXM at doses (60-120 pmol.kg-1.h-1) that induced physiological circulating levels inhibited gastric acid secretion up to 50%. Under meal stimulation, OXM reduced up to 29% acid secretion at doses (1-1.5 nmol.kg-1.h-1) inducing supraphysiological levels. We conclude that at physiological concentrations OXM cannot counteract the complex processes triggered by a meal. OXM would be a component of enterogastrone, a combination of several intestinal hormones acting in synergy. The OXM action is related to pathways recognizing the C-terminal 19-37 moiety of the molecule.