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2‐Naphthalenesulphonyl l ‐aspartyl‐(2‐phenethyl)amide (2‐NAP)‐a selective cholecystokinin CCK A ‐receptor antagonist
Author(s) -
Hull R.A.D.,
Shankley N.P.,
Harper E.A.,
Gerskowitch V.P.,
Black J.W.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb12870.x
Subject(s) - cholecystokinin , radioligand , chemistry , receptor , cholecystokinin receptor , receptor antagonist , antagonist , endocrinology , medicine , agonist , pharmacology , biology , biochemistry
1 The in vitro pharmacological characterization of the sodium salt of 2‐naphthalenesulphonyl l‐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 CCK A ‐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 p K B , over assays, was 6.5. 3 Compared to the other assays, the rabbit gall bladder assay gave a significantly higher p K B 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 CCK A ‐receptor antagonist; these anomalous results suggest that a different class of CCK A ‐receptors may be involved. 4 2‐NAP, was found to be highly selective, having at least 300 fold greater affinity for CCK A ‐receptors than for 50 other pharmacological loci, including gastrin/CCK B , as estimated by bioassay or radioligand displacement.