RT Journal Article
SR Electronic
T1 CholecystokininA and cholecystokininB receptors in neurons of the brainstem solitary complex of the rat: pharmacological identification.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1433
OP 1440
VO 260
IS 3
A1 P Branchereau
A1 G A Böhme
A1 J Champagnat
A1 M P Morin-Surun
A1 C Durieux
A1 J C Blanchard
A1 B P Roques
A1 M Denavit-Saubié
YR 1992
UL http://jpet.aspetjournals.org/content/260/3/1433.abstract
AB 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.