The intestinal hormone cholecystokinin (CCK) inhibits food intake via stimulation of vagal afferent neurons (VAN). Recent studies suggest CCK also regulates the expression of some G-protein coupled receptors and neuropeptide transmitters in these neurons. The aim of the present studies was to characterise the expression of cannabinoid (CB)1 receptors in VAN and to determine whether stimulation of these receptors plays a role in regulating neurochemical phenotype. Expression of CB1 in rat VAN was detectable by in situ hybridization or immunohistochemistry after 6 h of fasting and increased to a maximum after 24 h when approximately 50 % of neurons in the mid- and caudal regions expressed the receptor. Melanin concentrating hormone(MCH)1 receptors also increased with fasting but the changes were delayed compared with CB1; in contrast Y2R receptors exhibited reciprocal changes in expression to CB1. Administration of CCK8s (10nmol, ip) to fasted rats decreased expression of CB1 with a t1/2 of approximately 1 h compared with 3 h for MCH-1. The action of CCK8s was inhibited by ghrelin and orexin-A. The CB1 agonist anandamide (AEA, ip) reversed the effect of CCK8s on CB1, MCH1 and Y2 receptor expression. In contrast, in rats fasted for 18 h, administration of a CB1 antagonist/inverse agonist (AM281, ip) down-regulated CB1 expression and increased Y2 receptor expression. Activation of vagal CB1 receptors therefore influences the neurochemical phenotype of these neurons indicating a new and hitherto unrecognised role for endocannabinoids in gut-brain signalling.
- nodose ganglion
- MCH1 receptor
- Copyright © 2010, American Journal of Physiology- Gastrointestinal and Liver Physiology