CHARACTERIZATION OF CCK RECEPTORS IN A NOVEL SMOOTH-MUSCLE PREPARATION FROM THE GUINEA-PIG STOMACH BY USE OF THE SELECTIVE ANTAGONISTS CI-988, L-365,260 AND DEVAZEPIDE

1 The cholecystokinin receptors mediating motor responses in a novel smooth muscle preparation from the corpus region of the guinea-pig stomach have been characterized by use of five agonist peptides and the antagonists CI-988, L-365,260 and devazepide. 2 Mucosa-denuded strips of circular muscle were contracted in a concentration-dependent manner by the five cholecystokinin (CCK)-related peptides CCK-8S, pentagastrin, gastrin-1, CCK-8US and CCK-4. 3 CI-988 was a powerful antagonist of the response to pentagastrin with an affinity (Pk(B) = 9.49) similar to that obtained in CCK(B) receptor binding assays. With CCK-8S as the agonist, CI-988 was approximately 1000 fold less powerful as an antagonist. 4 Devazepide powerfully blocked responses to CCK-8S with an affinity (pK(B) = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCK(A) receptor activity. Devazepide displayed lower affinity against pentagastrin than against CCK-8S. 5 CI-988 blocked responses to pentagastrin in an insurmountable manner in the presence of 3 nM devazepide; a concentration previously shown to block the CCK(A) receptor. The nature of the antagonism observed with L-365,260 was unaltered by the presence of devazepide. 6 The guinea-pig stomach corpus smooth muscle preparation contains both subtypes of CCK receptor and will be useful as a pharmacological tool for investigating the functional effects of novel CCK ligands.