Pharmacological studies on CCKB receptors in guinea pig synaptoneurosomes.
Preliminary studies on CCK receptors in the central nervous system were carried out on guinea pig cerebral cortical synaptoneurosome preparations. In binding assays, the range of affinity of CCK-8, Boc-[Nle28,Nle31]CCK-7, a potent CCK analog, Boc-[Leu31]CCK-4 and of the two benzodiazepine CCK receptor antagonists L-365,260 and MK-329, is in agreement with the presence of CCKB receptors on this model. The effects of Boc-[Nle28,Nle31]CCK-7 on inositol phosphates, cAMP accumulation and 45Ca2+ efflux were investigated. Neither inositol phosphate nor cAMP accumulations could be observed. On the other hand, evidence of Boc-[Nle28,Nle31]CCK-7-, CCK-8- and Boc-[Leu31]CCK-4-induced 45Ca2+ efflux was found in a dose-dependent manner. The CCKB-selective receptor antagonist L-365,260 and, with a weaker efficiency, the CCKA-selective receptor antagonist MK-329, are able to block a maximal effect of Boc-[Nle28,Nle31]CCK-7-induced 45Ca2+ efflux, suggesting that CCKB receptors may regulate calcium ion mobilization.
Galas
M C
MC
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Faculté de Pharmacie, Montpellier, France.
Bernad
N
N
Martinez
J
J
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D020109:Devazepide; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D001570:Benzodiazepinones; D007295:Inositol Phosphates; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C060807:butyloxycarbonyl-tryptophyl-leucyl-aspartyl-phenylalaninamide; C058121:L 365260; D002766:Cholecystokinin; C047716:cholecystokinin (27-33), tert-butyloxycarbonyl-Nle(28,31)-; D000242:Cyclic AMP; D020109:Devazepide; D012844:Sincalide; D002118:Calcium