Involvement of cholecystokinin receptor types in pathways controlling oxytocin secretion.
1. Intravenous administration of cholecystokinin (CCK) results in a transient activation of oxytocin neurones in the rat, and hence to oxytocin secretion: this activation is followed by expression of c-fos mRNA and of Fos-like immunoreactivity (Fos-LI) in magnocellular oxytocin neurones. Fos-like immunoreactivity is also induced in the regions of the brainstem that are thought to relay information from the periphery to the hypothalamus. 2. Administration of the selective CCKA receptor antagonist MK-329, but not the CCKB receptor antagonist L-365,260, prior to CCK injection, prevented oxytocin release as measured by radioimmunoassay and oxytocin neuronal activation as measured by electrophysiology and by the lack of induction of c-fos mRNA. 3. MK-329 abolished the release of adrenocorticotrophic hormone (ACTH) following injection of CCK. 4. MK-329 prevented the expression of Fos-LI in the hypothalamic magnocellular nuclei and in the area postrema and dorsal vagal complex of the brainstem. 5. L-365,260 had no effect on the expression of Fos-LI in the brainstem, but attenuated that seen in the hypothalamic magnocellular nuclei. 6. We conclude that CCK acts on CCKA receptors, either in the area postrema or on peripheral endings of the vagus nerve, to cause the release of hypothalamic oxytocin and ACTH. Information may be carried to the hypothalamus in part by CCK acting at CCKB receptors.
Luckman
S M
SM
Department of Neurobiology, AFRC Babraham Institute, Cambridge.
Hamamura
M
M
Antonijevic
I
I
Dye
S
S
Leng
G
G
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000502:physiology; D001570:Benzodiazepinones / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020109:Devazepide; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D009474:Neurons / Q000502:physiology; D010121:Oxytocin / Q000097:blood*; D010671:Phenylurea Compounds; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C058121:L 365260; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D002766:Cholecystokinin; D020109:Devazepide