CCK-8-related C-terminal tetrapeptides: affinities for central CCKB and peripheral CCKA receptors

Eur J Pharmacol. 1991 Dec 17;209(3):263-6. doi: 10.1016/0014-2999(91)90180-x.

Abstract

We investigated the binding affinity of new tetrapeptides derived from the C-terminal sequence of CCK8 to central CCKB and peripheral CCKA receptors. Compound 1 (Boc-Trp-Met-Asp-Phe-NH2) showed high affinity for central CCKB receptors (Ki 4.2 x 10(-8) M, pancreas/cortex ratio = 283). Compounds 2 (Suc-Trp-Met-Asp-Phe-NH2) and 3 (Suc-Trp-Leu-Asp-Phe-NH2) also exhibited high affinity (Ki 2.7 x 10(-8) M and 5.6 x 10(-8) M, respectively) but their CCKB selectivity was nearly 50 times higher (Ki ratio greater than 14,000). Replacement of Met or Leu by other amino acids resulted in less effective tetrapeptides.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzodiazepinones / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cholecystokinin / antagonists & inhibitors
  • Cholecystokinin / chemistry
  • Cholecystokinin / metabolism*
  • Devazepide
  • Guinea Pigs
  • In Vitro Techniques
  • Kinetics
  • Molecular Sequence Data
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Peptides / pharmacology
  • Phenylurea Compounds*
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Receptors, Cholecystokinin / drug effects
  • Receptors, Cholecystokinin / metabolism*

Substances

  • Benzodiazepinones
  • Peptides
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • L 365260
  • Cholecystokinin
  • Devazepide