Oxyntomodulin Reduces Hydromineral Transport Through Rat Small Intestine

Abstract

Glicentin (GLIC) and oxyntomodulin (OXM) arereleased from the ileum and colon during digestion. Bothhormones reduce fluid and proton secretion in thestomach. The luminal concentration of sodium andchloride underlying the nutrient absorption, the effectof OXM on electrolyte transport through the smallintestine, was assessed in vivo using ligated loops andin vitro using Ussing chambers. In vivo , a zero transport state, estimated by the net water,chloride, and sodium fluxes, was observed when an 80 mMNaCl normoosmolar solution (274 mosm) was administeredintraluminally. Active secretion was observed with hyperosmotic challenge (474 mosm). Theamplitude of this active secretion increased 2.5- to3-fold when an electrogenic challenge (NaCl 40 mM) wassubstituted to the hyperosmotic one. OXM (800 fmol/ml plasma) did not modify the basal transport inthe duodenum or in the jejunum (t = 45 min). When activesecretion was induced by the hyperosmotic challenge, OXM(200 fmol/ml plasma) had no effect on duodenal or jejunal transport (t = 50 min). When activesecretion was induced by an electrogenic challenge, OXM(300 fmol/ml plasma) preferentially reduced thehydromineral transport in jejunum. In vitro , OXM also induced a reduction in the ion transporttowards the jejunal lumen (EC₅₀ = 20 pM), theamplitude of which depended upon the integrity of thetetrodotoxin-sensitive neurons. In conclusion, OXM wasable to reduce the large secretion induced in ratjejunum in vivo by an electrogenic gradient. In vitro,the antisecretory effect of OXM was partly mediated bythe neurons present in the intrajejunal wall.