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

Br J Pharmacol. 1993 Aug;109(4):913-7. doi: 10.1111/j.1476-5381.1993.tb13707.x.

Abstract

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-I, CCK-8US and CCK-4. 3. CI-988 was a powerful antagonist of the response to pentagastrin with an affinity (pKB = 9.49) similar to that obtained in CCKB 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 (pKB = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCKA 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 CCKA 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.

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Carbachol / pharmacology
  • Cholecystokinin / analogs & derivatives
  • Cholecystokinin / antagonists & inhibitors*
  • Cholecystokinin / pharmacology
  • Devazepide
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastrins / antagonists & inhibitors
  • Gastrins / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Male
  • Meglumine / analogs & derivatives*
  • Meglumine / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Phenylurea Compounds*
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Receptors, Cholecystokinin / drug effects
  • Receptors, Cholecystokinin / metabolism*
  • Stomach / drug effects

Substances

  • Benzodiazepinones
  • Gastrins
  • Indoles
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • PD 134308
  • L 365260
  • Meglumine
  • Carbachol
  • Cholecystokinin
  • Devazepide