EFFECTS OF INTRADUODENAL ADMINISTRATION OF A LOW-DOSE OF CHOLECYSTOKININ (CCK) ANTAGONIST (CR-1505) ON PLASMA CCK CONCENTRATION, INTESTINALCCK CONTENT, AND LEVELS OF CCK MESSENGER-RNA

The effects of the intraduodenal administration of a low dose of CR-15 05 for 3-7 days on the gene expression of cholecystokinin (CCK), plasm a CCK concentration, and CCK content in the intestinal mucosa were exa mined in rats. The simultaneous changes of protein and enzyme content in the pancreas were also determined. CR-1505 was infused continuously into the duodenum at a dose of 3 mg/kg per day, calculated to corresp ond to a dose of 150-200 mg/day in humans. Seven days after the admini stration of CR-1505, a liquid meal (4.5 kcal/3 ml) was introduced into the stomach and changes in the intestinal CCK content and plasma CCK concentration were examined. The level of CCK mRNA in the intestine wa s significantly higher in rats treated with CR-1505 than in control ra ts. The plasma CCK concentration, the CCK content of the intestinal mu cosa, and the composition of pancreatic enzymes did not significantly differ in rats treated with CR-1505 and the untreated controls. In con trol rats, the administration of the liquid meal increased the plasma CCK concentration and significantly decreased the intestinal CCK conte nt in water extracts, but did not affect the amount extracts in acid w hereas the ingestion of the meal did not cause any significant changes in rats treated with CR-1505. These findings indicate that a low dose of CR-1505 stimulates the gene expression of CCK without enhancing CC K release or exerting an effect on the pancreas.