CholecystokininA and cholecystokininB receptors in neurons of the brainstem solitary complex of the rat: pharmacological identification.
The brainstem solitary complex, which receives projections from primary sensory afferents of the vagus nerve, appears to be a crucial site for the action of the cholecystokinin octapeptide (CCK8), because both peripheral-type (CCKA) and central-type (CCKB) binding sites are present in this structure. In the present study, we investigated the effects of recently developed receptor-specific pharmacological tools on neurons recorded in rat coronal brainstem slices, to ascertain whether CCK acts differently on each type of receptor. CCK8, which interacts with both binding sites, had three effects on neuronal discharge, brief excitation, prolonged excitation and delayed inhibition. BC 264, a novel CCK analog endowed with high affinity and selectivity for CCKB receptors, produced exclusively prolonged excitation. L-365,260, a novel nonpeptide antagonist of CCKB receptors, blocked the prolonged excitation induced by BC 264 or CCK8. L-364,718, a potent antagonist of CCKA receptors, blocked delayed inhibition and replaced brief CCK8-induced excitation by prolonged excitation. Altogether, these results show that CCK8 exerts, on neurons of the solitary complex, mixed effects due to simultaneous activation of CCKA inhibitory and CCKB excitatory binding sites. The hypothesis that exogenous CCK8 acts, in the solitary complex, through CCKA sites to slow down the motility of the digestive tract and through CCKB sites to modulate anxiety will be developed.
Branchereau
P
P
Institut Alfred Fessard, CNRS, Gif-sur-Yvette, France.
Böhme
G A
GA
Champagnat
J
J
Morin-Surun
M P
MP
Durieux
C
C
Blanchard
J C
JC
Roques
B P
BP
Denavit-Saubié
M
M
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology; D020109:Devazepide; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology
C084553:BC 264; D001570:Benzodiazepinones; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide