Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin.
Both inhibitory (satiety) and stimulatory (orexigenic) factors from the gastrointestinal tract regulate food intake. In the case of the satiety hormone cholecystokinin (CCK), these effects are mediated via vagal afferent neurons. We now report that vagal afferent neurons expressing the CCK-1 receptor also express cannabinoid CB1 receptors. Retrograde tracing established that these neurons project to the stomach and duodenum. The expression of CB1 receptors determined by RT-PCR, immunohistochemistry and in situ hybridization in rat nodose ganglia was increased by withdrawal of food for > or =12 hr. After refeeding of fasted rats there was a rapid loss of CB1 receptor expression identified by immunohistochemistry and in situ hybridization. These effects were blocked by administration of the CCK-1 receptor antagonist lorglumide and mimicked by administration of CCK to fasted rats. Because CCK is a satiety factor that acts via the vagus nerve and CB1 agonists stimulate food intake, the data suggest a new mechanism modulating the effect on food intake of satiety signals from the gastrointestinal tract.
Burdyga
Galina
G
Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom.
Lal
Simon
S
Varro
Andrea
A
Dimaline
Rod
R
Thompson
David G
DG
Dockray
Graham J
GJ
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D046508:Culture Techniques; D004386:Duodenum / Q000294:innervation; D005508:Food Deprivation / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009409:Nerve Crush; D009475:Neurons, Afferent / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis / Q000235:genetics; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012528:Satiety Response / Q000502:physiology; D013270:Stomach / Q000294:innervation; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism*
D006727:Hormone Antagonists; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide