title: Electrophysiological studies of the cholecystokininA receptor antagonists SR27897B and PD140548 in the rat isolated nodose ganglion.
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 SR 27897B, were investigated in a convenient model system, the rat isolated nodose ganglion. CCK (1 nM-1 microM) caused concentration-dependent depolarisations when superfused over the nodose ganglion at 37 degrees 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 27897B (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 27897B 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 PD140548 are efficacious CCKA receptor antagonists.
authors: Department of Pharmacology, Monash University, Clayton Victoria, Australia.
authors: P M
authors: PM
authors: Beart
authors: E
authors: E
authors: Krstew
authors: R E
authors: RE
authors: Widdop
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006727:Hormone Antagonists / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000494:pharmacology*; D009620:Nodose Ganglion / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D006727:Hormone Antagonists; D007210:Indoleacetic Acids; D011949:Receptors, Cholecystokinin; D013844:Thiazoles; C080460:SR 27897