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

With increased interest in the pharmacology of cholecystokinin_A (CCK_A) receptors, including their trophic and mitogenic effects, the actions of two new non-peptide CCK_A 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 CCK_A 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 K_B 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 K_B 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 CCK_A-mediated responses, with the results indicating that both SR27897B and PD140548 are efficacious CCK_A receptor antagonists.