Electrophysiological studies of the cholecystokininA receptor antagonists SR27897B and PD140548 in the rat isolated nodose ganglion

Philip M. Beart, Elena Krstew, Robert E. Widdop

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Abstract

With increased interest in the pharmacology of cholecystokininA (CCKA) receptors, including their trophic and mitogenic effects, the actions of two new non-peptide CCKA receptor antagonists, PD140548 and SR27897B, were investigated in a convenient model system, the rat isolated nodose ganglion. CCK (1 nM-1 μM) caused concentration-dependent depolarisations when superfused over the nodose ganglion at 37°C as measured by a silicone grease gap technique, and both CCKA antagonists caused significant rightward shifts in the concentration response curve to CCK. SR27897B (3 and 10 nM) caused 7.9- and 17.9-fold shifts in the CCK concentration-response curve and the apparent - log KB values for each concentration of antagonist were calculated to be 9.36 and 9.23. Further experiments with PD140548 (30 and 100 nM) yielded shifts of 2.9- and 12.5-fold from which - log KB values were determined to be 7.80 and 8.06. Overall SR27897B was significantly more efficacious than PD140548. Thus, the isolated nodose ganglion preparation allows a functional assessment of CCKA-mediated responses, with the results indicating that both SR27897B and PD140548 are efficacious CCKA receptor antagonists.

Original languageEnglish
Pages (from-to)693-697
Number of pages5
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume353
Issue number6
DOIs
Publication statusPublished - 1 Jan 1996

Keywords

  • Cholecystokinin
  • Depolarisation
  • Rat nodose ganglion
  • Receptor antagonists
  • Receptor subtypes

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