Electrophysiological studies of the cholecystokininA receptor antagonists SR27897B and PD140548 in the rat isolated nodose ganglion.
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.
Beart
P M
PM
Department of Pharmacology, Monash University, Clayton Victoria, Australia.
Krstew
E
E
Widdop
R E
RE
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*
D006727:Hormone Antagonists; D007210:Indoleacetic Acids; D011949:Receptors, Cholecystokinin; D013844:Thiazoles; C080460:SR 27897