Dissociation of pancreozymin (PZ) activity from cholecystokinin (CCK) activity by N^α-carboxyacyl CCK7 and CCK8 analogues with a substituted glycine

Abstract

We have synthesized twelve CCK7 and CCK8 analogues with a substituted glycine at position 3 or 4. The most interesting analogues studied were N^α-carboxyacylated CCK7 or CCK8 with D-tryptophan or D-alanine substitution, i.e. N^α-carboxyacylated [D-Trp³]- and [D-Ala³]-CCK7 and N^α-carboxyacylated [D-Trp⁴]- and [D-Ala⁴]-CCK8. These analogues stimulated pancreatic exocrine secretion in anesthetized rats to almost the same extent as CCK8, but their guinea pig gall bladder contracting activity was substantially diminished. The selective stimulation of pancreatic secretion was also confirmed in vivo in anesthetized dogs with the D-amino acid-substituted CCK7 analogues.