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Combined dose‐ratio analysis of cholecystokinin receptor antagonists, devazepide, lorglumide and loxiglumide in the guinea‐pig gall bladder
Author(s) -
Bishop L.A.,
Gerskowitch V.P.,
Hull R.A.D.,
Shankley N.P.,
Black J.W.
Publication year - 1992
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.1476-5381.1992.tb14293.x
Subject(s) - cholecystokinin , cholecystokinin receptor , proglumide , medicine , endocrinology , pentagastrin , receptor , agonist , biology , population , chemistry , gastric acid , secretion , environmental health
1 Interactions between cholecystokinin octapeptide (CCK‐8) and CCK A ‐receptor antagonists derived from benzodiazepines (devazepide) and glutamic acid (lorglumide and loxiglumide) have been examined in an improved bioassay using the guinea‐pig, isolated, gall bladder preparation. 2 The presence of CCK B ‐receptors in the assay was provisionally‐ruled out on the basis of the low potency of pentagastrin in the assay. By applying analyses of both agonism and antagonism, pentagastrin was shown to behave as a partial agonist at the CCK A ‐receptor. 3 Devazepide, lorglumide and loxiglumide behaved as simple competitive antagonists of CCK A ‐receptors and p K B values of 9.98, 7.59 and 7.07 were estimated, respectively. 4 Application of a combined dose‐ratio analysis to the interactions between CCK‐8 and combinations of devazepide/lorglumide and devazepide/loxiglumide indicated that these molecules behave as syntopic, competitive, antagonists at the CCK A ‐receptor. 5 We conclude that the guinea‐pig gall bladder assay contains a homogeneous population of CCK A ‐receptors and offer an explanation for the differences between our results and those obtained recently by Maubach et al . (1991) which were taken as preliminary evidence for CCK A ‐receptor heterogeneity.