Heterogeneity of CCK-B receptors involved in animal models of anxiety.
The effects of the selective CCK-B agonists, BC 264 and BC 197, and the nonselective CCK agonist BDNL were investigated in the elevated plus-maze in rats. BDNL and BC 197 induced anxiogeniclike effects, in contrast to BC 264, which had no effect. The behavioral responses induced by BDNL were not significantly blocked by L-365,260, but were suppressed by CI-988, another selective CCK-B antagonist, and by high doses of L-364,718, a selective CCK-A antagonist. BC 197-induced effects were also blocked by CI-988. Competition experiments performed with [3H]pBC 264 using brain membranes of guinea pig, mouse, and rat were significantly better fitted when analyzed by a two site model than by a one site model with BC 197 but not with BC 264. Moreover, BC 264 produced anxiogeniclike effects when administered with increasing doses of L-365,260 and opposing effects with increasing doses of CI-988. Together these results give pharmacological and behavioral evidence for the existence of CCK-B receptor subtypes.
Derrien
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Département de Pharmacochimie Moléculaire et Structurale, INSERM U266 - CNRS URA D 1500 UFR des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie, Paris, France.
McCort-Tranchepain
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I
Ducos
B
B
Roques
B P
BP
Durieux
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000493:pharmacokinetics / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D020109:Devazepide; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
C084553:BC 264; D001570:Benzodiazepinones; D007211:Indoles; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C060186:BC 197; C065599:PD 134308; C058121:L 365260; D008536:Meglumine; D002766:Cholecystokinin; D020109:Devazepide