OXYNTOMODULIN REDUCES HYDROMINERAL TRANSPORT THROUGH RAT SMALL-INTESTINE

Glicentin (GLIC) and oxyntomodulin (OXM) are released from the ileum a nd colon during digestion. Both hormones reduce fluid and proton secre tion in the stomach. The luminal concentration of sodium and chloride underlying the nutrient absorption, the effect of OXM on electrolyte t ransport through the small intestine, was assessed in vivo using ligat ed loops and in vitro using Ussing chambers. In vivo, a zero transport stale, estimated by the net water, chloride, and sodium fluxes, was o bserved when an 80 mM NaCl normoosmolar solution (274 mosm) was admini stered intraluminally. Active secretion was observed with hyperosmotic challenge (474 mosm). The amplitude of this active secretion increase d 2.5- to 3-fold when an electrogenic challenge (NaCl 40 mM) was subst ituted to the hyperosmotic one. OXM (800 fmol/ml plasma) did not modif y the basal transport in the duodenum or in the jejunum (t = 45 min). When active secretion was induced by the hyperosmotic challenge, OXM ( 200 fmol/ml plasma) had no effect on duodenal or jejunal transport (t = 50 min). When active secretion was induced by an electrogenic challe nge, OXM (300 fmol/ml plasma) preferentially reduced the hydromineral transport in jejunum. In vitro, OXM also induced a reduction in the io n transport towards the jejunal lumen (EC50 = 20 pM), the amplitude of which depended upon the integrity of the tetrodotoxin-sensitive neuro ns. In conclusion, OXM was able to reduce the large secretion induced in rat jejunum in vivo by an electrogenic gradient. In vitro, the anti secretory effect of OXM was partly mediated by the neurons present in the intrajejunal wall.