2-Naphthalenesulphonyl L-aspartyl-(2-phenethyl)amide (2-NAP)--a selective cholecystokinin CCKA-receptor antagonist.
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.
Hull
R A
RA
James Black Foundation, King's College School of Medicine & Dentistry, London.
Shankley
N P
NP
Harper
E A
EA
Gerkowitch
V P
VP
Black
J W
JW
D000368:Aged; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D005704:Gallbladder / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009282:Naphthalenesulfonates / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D010418:Pentagastrin / Q000494:pharmacology; D011817:Rabbits; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013388:Succinimides
D009282:Naphthalenesulfonates; D011949:Receptors, Cholecystokinin; D013388:Succinimides; C080661:N-(2-naphthalenesulfonyl)aspartyl-(2-phenethyl)amide; D001224:Aspartic Acid; C022581:Bolton-Hunter reagent; D000681:Amylases; D010418:Pentagastrin