Indexed on: 01 May '96Published on: 01 May '96Published in: Naunyn-Schmiedeberg's Archives of Pharmacology
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 SR 2789713, 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. SR 2789713 (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 SR 2789713 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 SR 27897B and PD 140548 are efficacious CCKA receptor antagonists.