Inhibition of pancreatic protein secretion by fatty acids in rats. Partial isolation and purification of an anticholecystokinin-peptide (ACP)

Abstract

Recently, Laugier and Sarles (J.Physiol. 1977,=,81) showed that in conscious rats intraileal infusion of oleic acid induced an inhibition of pancreatic protein secretion which was transmitted by cross-circulation. Our aim was 1/ to study in conscious rats the mechanism of release of this inhibitory factor, 2/ to purify it from the pig ileum. RESULTS : 1/ An intraduodenal infusion of oleic acid or of ISO-Osmolar Oleate sodium soap stimulated both volume and Protein output during infusion. At the end of infusion, v01~1~1e returned slowly to basal values while protein concentration and output decreased progressively below basal values (inhibition of respectively -65% and -60% two hours after the end of the infusion). When pancreatic juice and bile were returned into the duodenum during the infusion, OleiC acid and olive oil induced also a delayed inhibition Of protein Output. This delayed inhibition was still found with carrylate (CE), but no more with butyrate (C4). 1so-osmolar (5%). hyperosmolar (30%) glucose and casein + pancreatic ]uice did not inhibit protein secretion. 2/ Crude Extracts have been obtained from the pig ileum by the techniques described by MUTT. After chromatography on SG25 (Fine) and on Bio-Gel P6 (100-200 Mesh), the active material has been purified by carboxymethyl cellulose. The active fraction was eluted in these conditions after V.I.P. and was free of enteroglucaqon and somatostatin. This fraction inhibited volume and protein output Of basal secretion of conscious rats. This inhibition was proportiol!al to the dose ; the calculated 050 of inhibition was 18.75 q kg-l. 25 g/kg inhibited also strongly protein output stimulated by CCK-PZ and secretine. AS the name of snticholecystokinln had been proposed for the f,ictor which inhibits gallbladder contraction in the dog and which is released 1 hour after a fatty meal, (Sarles E+ al., Nutr. et Dieta, 2, 223, 1960), the name of antlch(.lecystoklnin peptldc (ACP) is proposed.