BIOACTIVITY OF INTRADUODENALLY AND INTRAVENOUSLY INFUSED FRAGMENTS OFLUMINAL CHOLECYSTOKININ RELEASING-FACTOR (LCRF)

A luminal cholecystokinin releasing factor (LCRF), has been purified f rom intestinal secretion and found to have a mass of 8136 daltons. The amino-terminal 41 residues have been sequenced. Previous studies show ed that intraduodenal infusion of the synthetic amino-terminal 35 amin o acid peptide, LCRF1-35 significantly stimulated pancreatic protein a nd fluid secretion in conscious rats, but the peptide did not stimulat e amylase release from isolated, dispersed pancreatic acini. In the pr esent study, several fragments of LCRF were synthesized and tested for CCK-releasing activity (pancreatic protein secretion) to determine wh ether shorter fragments of LCRF exhibit the characteristic biological activity of native LCRF and synthetic LCRF1-35. Compounds tested were LCRF1-41, LCRF1-35, LCRF1-6, and LCRF11-25. Of the fragments shorter t han LCRF1-35, only LCRF11-25 but not LCRF1-6 had significant CCK relea sing activity. LCRF1-41 was equivalent to LCRF1-35 in potency and effi cacy. Intravenous and intraduodenal infusion of LCRF1-35 elicited near ly identical dose-response curves. (C) 1998 Elsevier Science B.V.