CCK modulates inhibitory synaptic transmission in the solitary complex through CCKB sites.
The CCKB antagonists L-365, 260 and PD134308 and the CCKA antagonist L-364, 718 were applied to neurones of the rat solitary complex (SC) isolated in brainstem slices, while recording either intracellularly or by whole-cell patch-clamp. The CCKB antagonists increased the amplitude of spontaneous or solitary tract-evoked Cl(-)-dependent inhibitory synaptic events by 25 +/- 5% in 5/7 neurones. These events were identified as (1) reversed spontaneous potentials, (2) reversed multisynaptic potentials and (3) outward currents blocked by the GABAA antagonist bicuculline. The CCKB antagonists had no postsynaptic action and increased excitatory synaptic events by 16 +/- 5% in only 3/9 neurones. The CCKA antagonist depolarized neurones but had no effect on synaptic events. Results suggest that CCK, released from the SC tissue, modulates GABAergic interneurones through CCKB sites. This mechanism could contribute to panic attacks, probably mediated by CCKB receptors.
Branchereau
P
P
Institut Alfred Fessard, CNRS, Gif-sur-Yvette, France.
Champagnat
J
J
Roques
B P
BP
Denavit-Saubie
M
M
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000378:metabolism; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D020109:Devazepide; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000378:metabolism; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010671:Phenylurea Compounds; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001570:Benzodiazepinones; D007211:Indoles; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C065599:PD 134308; C058121:L 365260; D005680:gamma-Aminobutyric Acid; D008536:Meglumine; D002766:Cholecystokinin; D020109:Devazepide; D001640:Bicuculline