2-Naphthalenesulphonyl L-aspartyl-(2-phenethyl)amide (2-NAP)--a selective cholecystokinin CCKA-receptor antagonist

Br J Pharmacol. 1993 Mar;108(3):734-40. doi: 10.1111/j.1476-5381.1993.tb12870.x.

Abstract

1. The in vitro pharmacological characterization of the sodium salt of 2-naphthalenesulphonyl 1-aspartyl-(2-phenethyl)amide [2-NAP], a hydrophilic compound derived from the C-terminal aspartate-phenylalanine dipeptide of cholecystokinin (CCK), is described. 2. 2-NAP behaved as a competitive antagonist of sulphated cholecystokinin octapeptide (CCK-8) at CCKA-receptors in both intact tissue bioassays (guinea-pig gall bladder, pancreas and ileum, human and rabbit gall bladder) and a radioligand displacement assay (guinea-pig pancreatic cells). The mean pKB, over assays, was 6.5. 3. Compared to the other assays, the rabbit gall bladder assay gave a significantly higher pKB estimate [7.0] for 2-NAP and a significantly lower estimate [8.9] for devazepide (formerly L-364,718 and MK-329), a well-characterized CCKA-receptor antagonist; these anomalous results suggest that a different class of CCKA-receptors may be involved. 4. 2-NAP, was found to be highly selective, having at least 300 fold greater affinity for CCKA-receptors than for 50 other pharmacological loci, including gastrin/CCKB, as estimated by bioassay or radioligand displacement.

MeSH terms

  • Aged
  • Amylases / metabolism
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / pharmacology
  • Binding, Competitive / drug effects
  • Gallbladder / drug effects
  • Guinea Pigs
  • Humans
  • Ileum / drug effects
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Naphthalenesulfonates / pharmacology*
  • Pancreas / enzymology
  • Pentagastrin / pharmacology
  • Rabbits
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Species Specificity
  • Structure-Activity Relationship
  • Succinimides

Substances

  • Naphthalenesulfonates
  • Receptors, Cholecystokinin
  • Succinimides
  • N-(2-naphthalenesulfonyl)aspartyl-(2-phenethyl)amide
  • Aspartic Acid
  • Bolton-Hunter reagent
  • Amylases
  • Pentagastrin